Donald Metcalf

Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome (2009)

Ng, Ashley P., Hyland, Craig D., Metcalf, Donald, Carmichael, Catherine L., Loughran, Stephen J., Di Rago, Ladina, ...

Down syndrome is characterized by multiple phenotypic manifestations associated with trisomy of chromosome 21. The transient myeloproliferative disorder and acute megakaryocytic leukemia associated...

Polycomb Repressive Complex 2 (PRC2) Restricts Hematopoietic Stem Cell Activity (2008)

Ian J. Majewski, Marnie E. Blewitt, Edward J. McManus, Melanie Bahlo, Adrienne A. Hilton, ...

Polycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development. Using mice with an...

Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells (2006)

Thomas, Tim, Corcoran, Lynn M., Gugasyan, Raffi, Dixon, Mathew P., Brodnicki, Thomas, Nutt, Stephen L., ...

Monocytic leukemia zinc finger protein (MOZ), a transcriptional coactivator and member of the MYST family of histone acetyltransferases, is the target of recurrent translocations in acute myeloid...

The combined absence of NF-kappa B1 and c-Rel reveals that overlapping roles for these transcription factors in the B cell lineage are restricted to the activation and function of mature cells (2002)

Pohl, Thomas, Gugasyan, Raffi, Grumont, Raelene J., Strasser, Andreas, Metcalf, Donald, Tarlinton, David, ...

Transcription factors NF-KB1 and c-Rel, individually dispensable during embryogenesis, serve similar, yet distinct, roles in the function of mature hemopoietic cells. Redundancy among Rel/ NF-KB...

The combined absence of the transcription factors Rel and RelA leads to multiple hemopoietic cell defects (1999)

Grossmann, Mathis, Metcalf, Donald, Merryfull, Julie, Beg, Amer, Baltimore, David, Gerondakis, Steve

Individual Rel/NF-kappa B transcription factors, although dispensable for the development and maturation of most hemopoietic cells, are critical regulators of normal immune function. Redundancy among...

Purification and Partial Amino Acid Sequence of Asialo Murine Granulocyte--Macrophage Colony Stimulating Factor (1985)

Sparrow, Lindsay G., Metcalf, Donald, Hunkapiller, Michael W., Hood, Leroy E., Burgess, Anthony W.

A procedure utilizing reversed-phase high-performance liquid chromatography is described for the purification of asialo granulocyte--macrophage colony stimulating factor (asialo-GM-CSF) from mouse...

Purification and Partial Amino Acid Sequence of Asialo Murine Granulocyte-Macrophage Colony Stimulating Factor (1985)

Sparrow, Lindsay G., Metcalf, Donald, Hunkapiller, Michael W., Hood, Leroy E., Burgess, Anthony W.

A procedure utilizing reversed-phase high-performance liquid chromatography is described for the purification of asialo granulocyte--macrophage colony stimulating factor (asialo-GM-CSF) from mouse...

The development of fatal myocarditis and polymyositis in mice heterozygous for IFN-γ and lacking the SOCS-1 gene

Metcalf, Donald, Di Rago, Ladina, Mifsud, Sandra, Hartley, Lynne, Alexander, Warren S.

Mice lacking the gene encoding the suppressor of cytokine signaling-1 (SOCS-1 −/−) and heterozygous for the IFN–γ gene (IFN-γ +/−) avoided the IFN-γ-dependent preweaning death of SOCS-1...

Twenty proteins containing a C-terminal SOCS box form five structural classes

Hilton, Douglas J., Richardson, Rachael T., Alexander, Warren S., Viney, Elizabeth M., Willson, Tracy A., Sprigg, Naomi S., ...

The four members of the recently identified suppressor of cytokines signaling family (SOCS-1, SOCS-2, SOCS-3, and CIS, where CIS is cytokine-inducible SH2-containing protein) appear, by various...

The combined absence of the transcription factors Rel and RelA leads to multiple hemopoietic cell defects

Grossmann, Mathis, Metcalf, Donald, Merryfull, Julie, Beg, Amer, Baltimore, David, Gerondakis, Steve

Individual Rel/NF-κB transcription factors, although dispensable for the development and maturation of most hemopoietic cells, are critical regulators of normal immune function. Redundancy among...

Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130

Nicholson, Sandra E., De Souza, David, Fabri, Louis J., Corbin, Jason, Willson, Tracy A., Zhang, Jian-Guo, ...

Suppressor of cytokine signaling-3 (SOCS-3) is one member of a family of intracellular inhibitors of signaling pathways initiated by cytokines that use, among others, the common receptor subunit...

Hematopoietic stem cell deficiencies in mice lacking c-Mpl, the receptor for thrombopoietin

Kimura, Shinya, Roberts, Andrew W., Metcalf, Donald, Alexander, Warren S.

Thrombopoietin (TPO) acts as a lineage-specific late-acting factor to stimulate megakaryocyte and platelet formation. However, analysis of mice lacking either the cytokine or its receptor, c-Mpl,...

Characterization of hematopoietic progenitor cells that express the transcription factor SCL, using a lacZ “knock-in” strategy

Elefanty, Andrew G., Begley, C. Glenn, Metcalf, Donald, Barnett, Louise, Köntgen, Frank, Robb, Lorraine

Gene targeting experiments have demonstrated that the transcription factor SCL is essential for primitive and definitive hematopoiesis in the mouse. To study the functional properties of...

Apoptosis regulator Bcl-w is essential for spermatogenesis but appears otherwise redundant

Print, Cristin G., Loveland, Kate L., Gibson, Leonie, Meehan, Terri, Stylianou, Anna, Wreford, Nigel, ...

Proteins of the Bcl-2 family are important regulators of apoptosis in many tissues of the embryo and adult. The recently isolated bcl-w gene encodes a pro-survival member of the Bcl-2 family, which...

Murine hematopoietic stem cells committed to macrophage/dendritic cell formation: Stimulation by Flk2-ligand with enhancement by regulators using the gp130 receptor chain

Metcalf, Donald

The stimulation by Flk2-ligand (FL) of blast colony formation by murine bone marrow cells was selectively potentiated by the addition of regulators sharing in common the gp130 signaling...

Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1

Starr, Robyn, Metcalf, Donald, Elefanty, Andrew G., Brysha, Marta, Willson, Tracy A., Nicola, Nicos A., ...

SOCS-1, a member of the suppressor of cytokine signaling (SOCS) family, was identified in a genetic screen for inhibitors of interleukin 6 signal transduction. SOCS-1 transcription is induced by...

Constitutive Bcl-2 expression throughout the hematopoietic compartment affects multiple lineages and enhances progenitor cell survival

Ogilvy, Sarah, Metcalf, Donald, Print, Cristin G., Bath, Mary L., Harris, Alan W., Adams, Jerry M.

Bcl-2, which can both reduce apoptosis and retard cell cycle entry, is thought to have important roles in hematopoiesis. To evaluate the impact of its ubiquitous overexpression within this system, we...

Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells

Gainsford, Timothy, Willson, Tracy A., Metcalf, Donald, Handman, Emanuela, McFarlane, Clare, Ng, Ashley, ...

Many cytokines exert their biological effect through members of the hemopoietin receptor family. Using degenerate oligonucleotides to the common WSXWS motif, we have cloned from human hemopoietic...

The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation

Zhang, Jian-Guo, Farley, Alison, Nicholson, Sandra E., Willson, Tracy A., Zugaro, Lisa M., Simpson, Richard J., ...

The suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of...

Lineage commitment in the progeny of murine hematopoietic preprogenitor cells: Influence of thrombopoietin and interleukin 5

Metcalf, Donald

Normal mouse marrow cells were stimulated by stem cell factor (SCF) to form dispersed or multicentric blast colonies containing progenitor cells committed to various hematopoietic lineages....

Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3

Roberts, Andrew W., Robb, Lorraine, Rakar, Steven, Hartley, Lynne, Cluse, Leonie, Nicola, Nicos A., ...

Mice lacking suppressor of cytokine signaling 3 (SOCS3) exhibited embryonic lethality with death occurring between days 11 and 13 of gestation. At this stage, SOCS3−/− embryos were slightly...

The SOCS box of suppressor of cytokine signaling-1 is important for inhibition of cytokine action in vivo

Zhang, Jian-Guo, Metcalf, Donald, Rakar, Steven, Asimakis, Maria, Greenhalgh, Christopher J., Willson, Tracy A., ...

Suppressor of Cytokine Signaling-1 (SOCS-1) is an essential physiological inhibitor of IFN-γ signaling. Mice lacking this gene die in the early postnatal period from a disease characterized by...

Functional Analysis of Asb-1 Using Genetic Modification in Mice

Kile, Benjamin T., Metcalf, Donald, Mifsud, Sandra, DiRago, Ladina, Nicola, Nicos A., Hilton, Douglas J., ...

The Asbs are a family of ankyrin repeat proteins that, along with four other protein families, contain a C-terminal SOCS box motif, which was first identified in the suppressor of cytokine signaling...

Polycystic kidneys and chronic inflammatory lesions are the delayed consequences of loss of the suppressor of cytokine signaling-1 (SOCS-1)

Metcalf, Donald, Mifsud, Sandra, Di Rago, Ladina, Nicola, Nicos A., Hilton, Douglas J., Alexander, Warren S.

Mice with inactivation of the gene encoding the suppressor of cytokine signaling-1 (SOCS-1) die in neonatal life with an IFN-γ-dependent inflammatory disease dominated by fatty degeneration and...

The combined absence of NF-κB1 and c-Rel reveals that overlapping roles for these transcription factors in the B cell lineage are restricted to the activation and function of mature cells

Pohl, Thomas, Gugasyan, Raffi, Grumont, Raelene J., Strasser, Andreas, Metcalf, Donald, Tarlinton, David, ...

Transcription factors NF-κB1 and c-Rel, individually dispensable during embryogenesis, serve similar, yet distinct, roles in the function of mature hemopoietic cells. Redundancy among Rel/NF-κB...

SOCS-6 Binds to Insulin Receptor Substrate 4, and Mice Lacking the SOCS-6 Gene Exhibit Mild Growth Retardation

Krebs, Danielle L., Uren, Rachel T., Metcalf, Donald, Rakar, Steven, Zhang, Jian-Guo, Starr, Robyn, ...

SOCS-6 is a member of the suppressor of cytokine signaling (SOCS) family of proteins (SOCS-1 to SOCS-7 and CIS) which each contain a central SH2 domain and a carboxyl-terminal SOCS box. SOCS-1,...

The Absence of Tssc6, a Member of the Tetraspanin Superfamily, Does Not Affect Lymphoid Development but Enhances In Vitro T-Cell Proliferative Responses

Tarrant, Jacqueline M., Groom, Joanna, Metcalf, Donald, Li, Ruili, Borobokas, Bette, Wright, Mark D., ...

The tetraspanins are a family of integral membrane proteins with four transmembrane domains. These molecules form multimolecular networks on the surfaces of many different cell types. Gene-targeting...

The lethal effects of transplantation of Socs1-/- bone marrow cells into irradiated adult syngeneic recipients

Metcalf, Donald, Mifsud, Sandra, Di Rago, Ladina, Alexander, Warren S.

Injection of neonatal bone marrow cells from mice lacking the gene encoding suppressor of cytokine signaling 1 (SOCS1) into irradiated syngeneic 129/Sv or C57BL/6 mice led to a decreased survival,...

The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12

Hall, Mark A., Curtis, David J., Metcalf, Donald, Elefanty, Andrew G., Sourris, K., Robb, Lorraine, ...

Gene targeting studies have shown that the transcription factor SCL is critically important for embryonic hematopoiesis, but the early lethality of SCL null mice has precluded the genetic analysis of...

Crowding-dependent production of colony-stimulating factors by cultured syngeneic or allogeneic hematopoietic cells

Metcalf, Donald, Di Rago, Ladina, Mifsud, Sandra

Mitogenic stimulation in vitro of mouse T lymphocytes induces the production of the hematopoietic cytokines granulocyte–macrophage colony-stimulating factor and IL-3. The present experiments showed...

Suppressor screen in Mpl-/- mice: c-Myb mutation causes supraphysiological production of platelets in the absence of thrombopoietin signaling

Carpinelli, Marina R., Hilton, Douglas J., Metcalf, Donald, Antonchuk, Jennifer L., Hyland, Craig D., Mifsud, Sandra L., ...

Genetic screens in lower organisms, particularly those that identify modifiers of preexisting genetic defects, have been used successfully to order components of complex signaling pathways. To date,...

SOCS5 Is Expressed in Primary B and T Lymphoid Cells but Is Dispensable for Lymphocyte Production and Function

Brender, Christine, Columbus, Ruth, Metcalf, Donald, Handman, Emanuela, Starr, Robyn, Huntington, Nick, ...

Suppressors of cytokine signaling (SOCSs) are key regulators of cytokine-induced responses in hematopoietic as well as nonhematopoietic cells. SOCS1 and SOCS3 have been shown to modulate T-cell...

Critical role for granulocyte colony-stimulating factor in inflammatory arthritis

Lawlor, Kate E., Campbell, Ian K., Metcalf, Donald, O'Donnell, Kristy, Van Nieuwenhuijze, Annemarie, Roberts, Andrew W., ...

Granulocyte colony-stimulating factor (G-CSF) is a well known regulator of granulopoiesis, but the role of endogenous G-CSF in inflammatory joint disease has not been explored. We studied the...

Development of hydrocephalus in mice lacking SOCS7

Krebs, Danielle L., Metcalf, Donald, Merson, Tobias D., Voss, Anne K., Thomas, Tim, Zhang, Jian-Guo, ...

SOCS7 is a member of the suppressor of cytokine signaling (SOCS) family of proteins (SOCS1-SOCS7 and CIS). SOCS proteins are composed of an N-terminal domain of variable length, a central Src...

SOCS2 negatively regulates growth hormone action in vitro and in vivo

Greenhalgh, Christopher J., Rico-Bautista, Elizabeth, Lorentzon, Mattias, Thaus, Anne L., Morgan, Phillip O., Willson, Tracy A., ...

Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30–50% increase in mature body size. Here we show that the SOCS2–/– phenotype is dependent upon the presence of...

Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling

Nicholson, Sandra E., Metcalf, Donald, Sprigg, Naomi S., Columbus, Ruth, Walker, Francesca, Silva, Anabel, ...

The suppressors of cytokine signaling (SOCS) proteins are a family of SH2 domain-containing intracellular inhibitors of cytokine signal transduction that act by several different mechanisms. Recent...

Granulocyte/macrophage-, megakaryocyte-, eosinophil- and erythroid-colony-stimulating factors produced by mouse spleen cells

Burgess, Antony W., Metcalf, Donald, Russell, Sue H. M., Nicola, Nicos A.

The formation of mature haemopoietic cells is controlled by hormones that specifically stimulate the progenitor cells of the granulocyte/macrophage, eosinophil, megakaryocyte and erythroid pathways....

Genetic reduction of embryonic leukemia-inhibitory factor production rescues placentation in SOCS3-null embryos but does not prevent inflammatory disease

Robb, Lorraine, Boyle, Kristy, Rakar, Steven, Hartley, Lynne, Lochland, Janelle, Roberts, Andrew W., ...

The suppressor of cytokine-signaling (SOCS) proteins act as negative-feedback inhibitors of cytokine and growth-factor-induced signal transduction. In vivo studies have implicated SOCS3 as a negative...

Inactivation of PU.1 in adult mice leads to the development of myeloid leukemia

Metcalf, Donald, Dakic, Aleksandar, Mifsud, Sandra, Di Rago, Ladina, Wu, Li, Nutt, Stephen

Genetically primed adult C57BL mice were deleted of exon 5 of the gene encoding the transcription factor PU.1 by IFN activation of Cre recombinase. After a 13-week delay, conditionally deleted...

Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells

Thomas, Tim, Corcoran, Lynn M., Gugasyan, Raffi, Dixon, Mathew P., Brodnicki, Thomas, Nutt, Stephen L., ...

Monocytic leukemia zinc finger protein (MOZ), a transcriptional coactivator and member of the MYST family of histone acetyltransferases, is the target of recurrent translocations in acute myeloid...

The development of fatal myocarditis and polymyositis in mice heterozygous for IFN-γ and lacking the SOCS-1 gene

Metcalf, Donald, Di Rago, Ladina, Mifsud, Sandra, Hartley, Lynne, Alexander, Warren S.

Mice lacking the gene encoding the suppressor of cytokine signaling-1 (SOCS-1 −/−) and heterozygous for the IFN–γ gene (IFN-γ +/−) avoided the IFN-γ-dependent preweaning death of SOCS-1...

Twenty proteins containing a C-terminal SOCS box form five structural classes

Hilton, Douglas J., Richardson, Rachael T., Alexander, Warren S., Viney, Elizabeth M., Willson, Tracy A., Sprigg, Naomi S., ...

The four members of the recently identified suppressor of cytokines signaling family (SOCS-1, SOCS-2, SOCS-3, and CIS, where CIS is cytokine-inducible SH2-containing protein) appear, by various...

The combined absence of the transcription factors Rel and RelA leads to multiple hemopoietic cell defects

Grossmann, Mathis, Metcalf, Donald, Merryfull, Julie, Beg, Amer, Baltimore, David, Gerondakis, Steve

Individual Rel/NF-κB transcription factors, although dispensable for the development and maturation of most hemopoietic cells, are critical regulators of normal immune function. Redundancy among...

Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130

Nicholson, Sandra E., De Souza, David, Fabri, Louis J., Corbin, Jason, Willson, Tracy A., Zhang, Jian-Guo, ...

Suppressor of cytokine signaling-3 (SOCS-3) is one member of a family of intracellular inhibitors of signaling pathways initiated by cytokines that use, among others, the common receptor subunit...

Hematopoietic stem cell deficiencies in mice lacking c-Mpl, the receptor for thrombopoietin

Kimura, Shinya, Roberts, Andrew W., Metcalf, Donald, Alexander, Warren S.

Thrombopoietin (TPO) acts as a lineage-specific late-acting factor to stimulate megakaryocyte and platelet formation. However, analysis of mice lacking either the cytokine or its receptor, c-Mpl,...

Characterization of hematopoietic progenitor cells that express the transcription factor SCL, using a lacZ “knock-in” strategy

Elefanty, Andrew G., Begley, C. Glenn, Metcalf, Donald, Barnett, Louise, Köntgen, Frank, Robb, Lorraine

Gene targeting experiments have demonstrated that the transcription factor SCL is essential for primitive and definitive hematopoiesis in the mouse. To study the functional properties of...

Apoptosis regulator Bcl-w is essential for spermatogenesis but appears otherwise redundant

Print, Cristin G., Loveland, Kate L., Gibson, Leonie, Meehan, Terri, Stylianou, Anna, Wreford, Nigel, ...

Proteins of the Bcl-2 family are important regulators of apoptosis in many tissues of the embryo and adult. The recently isolated bcl-w gene encodes a pro-survival member of the Bcl-2 family, which...

Murine hematopoietic stem cells committed to macrophage/dendritic cell formation: Stimulation by Flk2-ligand with enhancement by regulators using the gp130 receptor chain

Metcalf, Donald

The stimulation by Flk2-ligand (FL) of blast colony formation by murine bone marrow cells was selectively potentiated by the addition of regulators sharing in common the gp130 signaling...

Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1

Starr, Robyn, Metcalf, Donald, Elefanty, Andrew G., Brysha, Marta, Willson, Tracy A., Nicola, Nicos A., ...

SOCS-1, a member of the suppressor of cytokine signaling (SOCS) family, was identified in a genetic screen for inhibitors of interleukin 6 signal transduction. SOCS-1 transcription is induced by...

Constitutive Bcl-2 expression throughout the hematopoietic compartment affects multiple lineages and enhances progenitor cell survival

Ogilvy, Sarah, Metcalf, Donald, Print, Cristin G., Bath, Mary L., Harris, Alan W., Adams, Jerry M.

Bcl-2, which can both reduce apoptosis and retard cell cycle entry, is thought to have important roles in hematopoiesis. To evaluate the impact of its ubiquitous overexpression within this system, we...

Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells

Gainsford, Timothy, Willson, Tracy A., Metcalf, Donald, Handman, Emanuela, McFarlane, Clare, Ng, Ashley, ...

Many cytokines exert their biological effect through members of the hemopoietin receptor family. Using degenerate oligonucleotides to the common WSXWS motif, we have cloned from human hemopoietic...

The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation

Zhang, Jian-Guo, Farley, Alison, Nicholson, Sandra E., Willson, Tracy A., Zugaro, Lisa M., Simpson, Richard J., ...

The suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of...

Lineage commitment in the progeny of murine hematopoietic preprogenitor cells: Influence of thrombopoietin and interleukin 5

Metcalf, Donald

Normal mouse marrow cells were stimulated by stem cell factor (SCF) to form dispersed or multicentric blast colonies containing progenitor cells committed to various hematopoietic lineages....

Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3

Roberts, Andrew W., Robb, Lorraine, Rakar, Steven, Hartley, Lynne, Cluse, Leonie, Nicola, Nicos A., ...

Mice lacking suppressor of cytokine signaling 3 (SOCS3) exhibited embryonic lethality with death occurring between days 11 and 13 of gestation. At this stage, SOCS3−/− embryos were slightly...

The SOCS box of suppressor of cytokine signaling-1 is important for inhibition of cytokine action in vivo

Zhang, Jian-Guo, Metcalf, Donald, Rakar, Steven, Asimakis, Maria, Greenhalgh, Christopher J., Willson, Tracy A., ...

Suppressor of Cytokine Signaling-1 (SOCS-1) is an essential physiological inhibitor of IFN-γ signaling. Mice lacking this gene die in the early postnatal period from a disease characterized by...

Functional Analysis of Asb-1 Using Genetic Modification in Mice

Kile, Benjamin T., Metcalf, Donald, Mifsud, Sandra, DiRago, Ladina, Nicola, Nicos A., Hilton, Douglas J., ...

The Asbs are a family of ankyrin repeat proteins that, along with four other protein families, contain a C-terminal SOCS box motif, which was first identified in the suppressor of cytokine signaling...

Polycystic kidneys and chronic inflammatory lesions are the delayed consequences of loss of the suppressor of cytokine signaling-1 (SOCS-1)

Metcalf, Donald, Mifsud, Sandra, Di Rago, Ladina, Nicola, Nicos A., Hilton, Douglas J., Alexander, Warren S.

Mice with inactivation of the gene encoding the suppressor of cytokine signaling-1 (SOCS-1) die in neonatal life with an IFN-γ-dependent inflammatory disease dominated by fatty degeneration and...

The combined absence of NF-κB1 and c-Rel reveals that overlapping roles for these transcription factors in the B cell lineage are restricted to the activation and function of mature cells

Pohl, Thomas, Gugasyan, Raffi, Grumont, Raelene J., Strasser, Andreas, Metcalf, Donald, Tarlinton, David, ...

Transcription factors NF-κB1 and c-Rel, individually dispensable during embryogenesis, serve similar, yet distinct, roles in the function of mature hemopoietic cells. Redundancy among Rel/NF-κB...

SOCS-6 Binds to Insulin Receptor Substrate 4, and Mice Lacking the SOCS-6 Gene Exhibit Mild Growth Retardation

Krebs, Danielle L., Uren, Rachel T., Metcalf, Donald, Rakar, Steven, Zhang, Jian-Guo, Starr, Robyn, ...

SOCS-6 is a member of the suppressor of cytokine signaling (SOCS) family of proteins (SOCS-1 to SOCS-7 and CIS) which each contain a central SH2 domain and a carboxyl-terminal SOCS box. SOCS-1,...

The Absence of Tssc6, a Member of the Tetraspanin Superfamily, Does Not Affect Lymphoid Development but Enhances In Vitro T-Cell Proliferative Responses

Tarrant, Jacqueline M., Groom, Joanna, Metcalf, Donald, Li, Ruili, Borobokas, Bette, Wright, Mark D., ...

The tetraspanins are a family of integral membrane proteins with four transmembrane domains. These molecules form multimolecular networks on the surfaces of many different cell types. Gene-targeting...

The lethal effects of transplantation of Socs1-/- bone marrow cells into irradiated adult syngeneic recipients

Metcalf, Donald, Mifsud, Sandra, Di Rago, Ladina, Alexander, Warren S.

Injection of neonatal bone marrow cells from mice lacking the gene encoding suppressor of cytokine signaling 1 (SOCS1) into irradiated syngeneic 129/Sv or C57BL/6 mice led to a decreased survival,...

The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12

Hall, Mark A., Curtis, David J., Metcalf, Donald, Elefanty, Andrew G., Sourris, K., Robb, Lorraine, ...

Gene targeting studies have shown that the transcription factor SCL is critically important for embryonic hematopoiesis, but the early lethality of SCL null mice has precluded the genetic analysis of...

Crowding-dependent production of colony-stimulating factors by cultured syngeneic or allogeneic hematopoietic cells

Metcalf, Donald, Di Rago, Ladina, Mifsud, Sandra

Mitogenic stimulation in vitro of mouse T lymphocytes induces the production of the hematopoietic cytokines granulocyte–macrophage colony-stimulating factor and IL-3. The present experiments showed...

Suppressor screen in Mpl-/- mice: c-Myb mutation causes supraphysiological production of platelets in the absence of thrombopoietin signaling

Carpinelli, Marina R., Hilton, Douglas J., Metcalf, Donald, Antonchuk, Jennifer L., Hyland, Craig D., Mifsud, Sandra L., ...

Genetic screens in lower organisms, particularly those that identify modifiers of preexisting genetic defects, have been used successfully to order components of complex signaling pathways. To date,...

SOCS5 Is Expressed in Primary B and T Lymphoid Cells but Is Dispensable for Lymphocyte Production and Function

Brender, Christine, Columbus, Ruth, Metcalf, Donald, Handman, Emanuela, Starr, Robyn, Huntington, Nick, ...

Suppressors of cytokine signaling (SOCSs) are key regulators of cytokine-induced responses in hematopoietic as well as nonhematopoietic cells. SOCS1 and SOCS3 have been shown to modulate T-cell...

Critical role for granulocyte colony-stimulating factor in inflammatory arthritis

Lawlor, Kate E., Campbell, Ian K., Metcalf, Donald, O'Donnell, Kristy, Van Nieuwenhuijze, Annemarie, Roberts, Andrew W., ...

Granulocyte colony-stimulating factor (G-CSF) is a well known regulator of granulopoiesis, but the role of endogenous G-CSF in inflammatory joint disease has not been explored. We studied the...

Development of hydrocephalus in mice lacking SOCS7

Krebs, Danielle L., Metcalf, Donald, Merson, Tobias D., Voss, Anne K., Thomas, Tim, Zhang, Jian-Guo, ...

SOCS7 is a member of the suppressor of cytokine signaling (SOCS) family of proteins (SOCS1-SOCS7 and CIS). SOCS proteins are composed of an N-terminal domain of variable length, a central Src...

SOCS2 negatively regulates growth hormone action in vitro and in vivo

Greenhalgh, Christopher J., Rico-Bautista, Elizabeth, Lorentzon, Mattias, Thaus, Anne L., Morgan, Phillip O., Willson, Tracy A., ...

Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30–50% increase in mature body size. Here we show that the SOCS2–/– phenotype is dependent upon the presence of...

Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling

Nicholson, Sandra E., Metcalf, Donald, Sprigg, Naomi S., Columbus, Ruth, Walker, Francesca, Silva, Anabel, ...

The suppressors of cytokine signaling (SOCS) proteins are a family of SH2 domain-containing intracellular inhibitors of cytokine signal transduction that act by several different mechanisms. Recent...

Granulocyte/macrophage-, megakaryocyte-, eosinophil- and erythroid-colony-stimulating factors produced by mouse spleen cells

Burgess, Antony W., Metcalf, Donald, Russell, Sue H. M., Nicola, Nicos A.

The formation of mature haemopoietic cells is controlled by hormones that specifically stimulate the progenitor cells of the granulocyte/macrophage, eosinophil, megakaryocyte and erythroid pathways....

Genetic reduction of embryonic leukemia-inhibitory factor production rescues placentation in SOCS3-null embryos but does not prevent inflammatory disease

Robb, Lorraine, Boyle, Kristy, Rakar, Steven, Hartley, Lynne, Lochland, Janelle, Roberts, Andrew W., ...

The suppressor of cytokine-signaling (SOCS) proteins act as negative-feedback inhibitors of cytokine and growth-factor-induced signal transduction. In vivo studies have implicated SOCS3 as a negative...

Inactivation of PU.1 in adult mice leads to the development of myeloid leukemia

Metcalf, Donald, Dakic, Aleksandar, Mifsud, Sandra, Di Rago, Ladina, Wu, Li, Nutt, Stephen

Genetically primed adult C57BL mice were deleted of exon 5 of the gene encoding the transcription factor PU.1 by IFN activation of Cre recombinase. After a 13-week delay, conditionally deleted...

Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells

Thomas, Tim, Corcoran, Lynn M., Gugasyan, Raffi, Dixon, Mathew P., Brodnicki, Thomas, Nutt, Stephen L., ...

Monocytic leukemia zinc finger protein (MOZ), a transcriptional coactivator and member of the MYST family of histone acetyltransferases, is the target of recurrent translocations in acute myeloid...

Neutralization of interferon-γ in neonatal SOCS1−/− mice prevents fatty degeneration of the liver but not subsequent fatal inflammatory disease

Bullen, Denise V R, Darwiche, Rima, Metcalf, Donald, Handman, Emanuela, Alexander, Warren S

Mice lacking the suppressor of cytokine signalling-1 (SOCS1) die within weeks of birth with extensive fatty degeneration of the liver, consistent with acute hepatic toxicity to interferon-γ...

A mutation in the translation initiation codon of Gata-1 disrupts megakaryocyte maturation and causes thrombocytopenia

Majewski, Ian J., Metcalf, Donald, Mielke, Lisa A., Krebs, Danielle L., Ellis, Sarah, Carpinelli, Marina R., ...

We have generated mice from a N-ethyl-N-nitrosourea mutagenesis screen that carry a mutation in the translation initiation codon of Gata-1, termed Plt13, which is equivalent to mutations found in...

Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 gene

Alexander, Warren S., Viney, Elizabeth M., Zhang, Jian-Guo, Metcalf, Donald, Kauppi, Maria, Hyland, Craig D., ...

An N-ethyl-N-nitrosourea mutagenesis screen in mice was performed to isolate regulators of circulating platelet number. We report here recessive thrombocytopenia and kidney disease in plt1 mice,...

Enforced expression of the homeobox gene Mixl1 impairs hematopoietic differentiation and results in acute myeloid leukemia

Glaser, Stefan, Metcalf, Donald, Wu, Li, Hart, Adam H., DiRago, Ladina, Mifsud, Sandra, ...

Mixl1, the sole murine homologue of the Xenopus Mix/Bix family of homeobox transcription factors, is essential for the patterning of axial mesendodermal structures during early embryogenesis. Gene...

FADD and caspase-8 are required for cytokine-induced proliferation of hemopoietic progenitor cells

Pellegrini, Marc, Bath, Sue, Marsden, Vanessa S., Huang, David C. S., Metcalf, Donald, Harris, Alan W., ...

The role of caspase-8 and its adaptor Fas-associated death domain (FADD) in lymphocyte apoptosis is well defined, but their functions in other hemopoietic lineages are not clear. We were unable to...

Cytotoxicity in vitro of preleukaemic lymphoid cells on syngeneic monolayers of embryo or thymus cells

Wahren, Britta, Metcalf, Donald

Lymphoid cells from preleukaemic AKR mice were cytotoxic for monolayers of syngeneic embryo and thymus target cells in tissue culture. This reactivity was detectable with cells from mice aged 3–36...

MYC levels govern hematopoietic tumor type and latency in transgenic mice

Smith, Darrin P., Bath, Mary L., Metcalf, Donald, Harris, Alan W., Cory, Suzanne

Deregulated MYC expression has been implicated in the etiology of many human cancers, including hematopoietic malignancies. To explore the impact of widespread constitutive MYC expression in the...

Agm1/Pgm3-Mediated Sugar Nucleotide Synthesis Is Essential for Hematopoiesis and Development▿

Greig, Kylie T., Antonchuk, Jennifer, Metcalf, Donald, Morgan, Phillip O., Krebs, Danielle L., Zhang, Jian-Guo, ...

Carbohydrate modification of proteins includes N-linked and O-linked glycosylation, proteoglycan formation, glycosylphosphatidylinositol anchor synthesis, and O-GlcNAc modification. Each of these...

Dynamic regulation of PU.1 expression in multipotent hematopoietic progenitors

Nutt, Stephen L., Metcalf, Donald, D'Amico, Angela, Polli, Matthew, Wu, Li

PU.1 is an Ets family transcription factor that is essential for fetal liver hematopoiesis. We have generated a PU.1gfp reporter strain that allowed us to examine the expression of PU.1 in all...

PU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis

Dakic, Aleksandar, Metcalf, Donald, Di Rago, Ladina, Mifsud, Sandra, Wu, Li, Nutt, Stephen L.

Although the transcription factor PU.1 is essential for fetal lymphomyelopoiesis, we unexpectedly found that elimination of the gene in adult mice allowed disturbed hematopoiesis, dominated by...

INDUCTION OF BONE MARROW COLONY-STIMULATING ACTIVITY BY A FILTERABLE AGENT IN LEUKEMIC AND NORMAL MOUSE SERUM

Foster, Roger, Metcalf, Donald, Kirchmyer, Rosemary

1. Leukemic Swiss mice of ICR/Ha strain which had been injected at birth with a lymphoid-leukemia-inducing virus preparation yielded sera which produced elevations of serum colony-stimulating...

Clonogenic mast cell progenitors and their excess numbers in chimeric BALB/c mice with inactivated GATA-1

Metcalf, Donald, Majewski, Ian, Mifsud, Sandra, Di Rago, Ladina, Alexander, Warren S.

In agar cultures of marrow cells from adult female BALB/c chimeric GATA-1Plt13/+ mice, a high frequency of unusual dispersed colonies was noted. Analysis showed that these were colonies of mast cells...

Blocking LIF action in the uterus by using a PEGylated antagonist prevents implantation: A nonhormonal contraceptive strategy

White, Christine A., Zhang, Jian-Guo, Salamonsen, Lois A., Baca, Manuel, Fairlie, W. Douglas, Metcalf, Donald, ...

Blastocyst implantation is a critical stage in the establishment of pregnancy. Leukemia inhibitory factor (LIF) is essential for mouse blastocyst implantation and also plays a role in human...

The preleukemic state of mice reconstituted with Mixl1-transduced marrow cells

Metcalf, Donald, Glaser, Stefan, Mifsud, Sandra, Di Rago, Ladina, Robb, Lorraine

Murine granulocytic cells, in becoming leukemic, need to acquire enhanced self-generation and a capacity for autocrine growth stimulation. Mice transplanted with bone marrow cells transduced with the...

Oct2 enhances antibody-secreting cell differentiation through regulation of IL-5 receptor α chain expression on activated B cells

Emslie, Dianne, D'Costa, Kathy, Hasbold, Jhagvaral, Metcalf, Donald, Takatsu, Kiyoshi, Hodgkin, Philip O., ...

Mice lacking a functional gene for the Oct2 transcriptional activator display several developmental and functional deficiencies in the B lymphocyte lineage. These include defective B cell receptor...

The SOCS box of suppressor of cytokine signaling-3 contributes to the control of G-CSF responsiveness in vivo

Boyle, Kristy, Egan, Paul, Rakar, Steven, Willson, Tracy A., Wicks, Ian P., Metcalf, Donald, ...

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of granulocyte-colony stimulating factor (G-CSF) signaling in vivo. SOCS proteins regulate cytokine signaling by binding, via their...

Hematopoietic cytokines

Metcalf, Donald

The production of hematopoietic cells is under the tight control of a group of hematopoietic cytokines. Each cytokine has multiple actions mediated by receptors whose cytoplasmic domains contain...

AGM: maternity ward or finishing school?

Metcalf, Donald

In this issue of Blood, Lux and colleagues and Ghiaur and colleagues shed new light on the controversy of whether hematopoietic stem cells (HSCs) arise in the yolk sac (YS) or the...

Polycomb Repressive Complex 2 (PRC2) Restricts Hematopoietic Stem Cell Activity

Majewski, Ian J, Blewitt, Marnie E, De Graaf, Carolyn A, McManus, Edward J, Bahlo, Melanie, Hilton, Adrienne A, ...

Polycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development. Using mice with an...

Point mutation in the gene encoding p300 suppresses thrombocytopenia in Mpl−/− mice

Kauppi, Maria, Murphy, James M., De Graaf, Carolyn A., Hyland, Craig D., Greig, Kylie T., Metcalf, Donald, ...

In an N-nitroso-N-ethylurea (ENU) mutagenesis screen using Mpl−/− mice, we isolated a semidominant suppressor of thrombocytopenia, termed Plt6. The gene mutated in Plt6 mice encodes the...