The Experts below are selected from a list of 21 Experts worldwide ranked by ideXlab platform
Samantha R Oakes - One of the best experts on this subject based on the ideXlab platform.
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a mutation in the viral sensor 2 5 oligoadenylate synthetase 2 causes Failure of Lactation
PLOS Genetics, 2017Co-Authors: Samantha R Oakes, David Gallegoortega, Prudence M Stanford, Simon Junankar, Zoya Kikhtyak, Anita Von Korff, Claudio M SergioAbstract:We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum Failure of Lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating Lactation.
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socs2 and elf5 mediate prolactin induced mammary gland development
Molecular Endocrinology, 2006Co-Authors: Jessica Harris, Samantha R Oakes, Prudence M Stanford, Kate D Sutherland, Matthew J Naylor, Fiona Robertson, Katrina Blazek, Michael Kazlauskas, Heidi N Hilton, Sergio WittlinAbstract:The proliferative phase of mammary alveolar morphogenesis is initiated during early pregnancy by rising levels of serum prolactin and progesterone, establishing a program of gene expression that is ultimately responsible for the development of the lobuloalveoli and the onset of Lactation. To explore this largely unknown genetic program, we constructed transcript profiles derived from transplanted mammary glands formed by recombination of prolactin receptor (Prlr) knockout or wild-type mammary epithelium with wild-type mammary stroma. Comparison with profiles derived from prolactin-treated Scp2 mammary epithelial cells produced a small set of commonly prolactin-regulated genes that included the negative regulator of cytokine signaling, Socs2 (suppressor of cytokine signaling 2), and the ets transcription factor, E74-like factor 5 (Elf5). Homozygous null mutation of Socs2 rescued the Failure of Lactation and reduction of mammary signal transducer and activator of transcription 5 phosphorylation that characterizes Prlr heterozygous mice, demonstrating that mammary Socs2 is a key regulator of the prolactin-signaling pathway. Reexpression of Elf5 in Prlr nullizygous mammary epithelium restored lobuloalveolar development and milk production, demonstrating that Elf5 is a transcription factor capable of substituting for prolactin signaling. Thus, Socs2 and Elf5 are key members of the set of prolactin-regulated genes that mediate prolactin-driven mammary development.
Claudio M Sergio - One of the best experts on this subject based on the ideXlab platform.
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a mutation in the viral sensor 2 5 oligoadenylate synthetase 2 causes Failure of Lactation
PLOS Genetics, 2017Co-Authors: Samantha R Oakes, David Gallegoortega, Prudence M Stanford, Simon Junankar, Zoya Kikhtyak, Anita Von Korff, Claudio M SergioAbstract:We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum Failure of Lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating Lactation.
Prudence M Stanford - One of the best experts on this subject based on the ideXlab platform.
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a mutation in the viral sensor 2 5 oligoadenylate synthetase 2 causes Failure of Lactation
PLOS Genetics, 2017Co-Authors: Samantha R Oakes, David Gallegoortega, Prudence M Stanford, Simon Junankar, Zoya Kikhtyak, Anita Von Korff, Claudio M SergioAbstract:We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum Failure of Lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating Lactation.
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socs2 and elf5 mediate prolactin induced mammary gland development
Molecular Endocrinology, 2006Co-Authors: Jessica Harris, Samantha R Oakes, Prudence M Stanford, Kate D Sutherland, Matthew J Naylor, Fiona Robertson, Katrina Blazek, Michael Kazlauskas, Heidi N Hilton, Sergio WittlinAbstract:The proliferative phase of mammary alveolar morphogenesis is initiated during early pregnancy by rising levels of serum prolactin and progesterone, establishing a program of gene expression that is ultimately responsible for the development of the lobuloalveoli and the onset of Lactation. To explore this largely unknown genetic program, we constructed transcript profiles derived from transplanted mammary glands formed by recombination of prolactin receptor (Prlr) knockout or wild-type mammary epithelium with wild-type mammary stroma. Comparison with profiles derived from prolactin-treated Scp2 mammary epithelial cells produced a small set of commonly prolactin-regulated genes that included the negative regulator of cytokine signaling, Socs2 (suppressor of cytokine signaling 2), and the ets transcription factor, E74-like factor 5 (Elf5). Homozygous null mutation of Socs2 rescued the Failure of Lactation and reduction of mammary signal transducer and activator of transcription 5 phosphorylation that characterizes Prlr heterozygous mice, demonstrating that mammary Socs2 is a key regulator of the prolactin-signaling pathway. Reexpression of Elf5 in Prlr nullizygous mammary epithelium restored lobuloalveolar development and milk production, demonstrating that Elf5 is a transcription factor capable of substituting for prolactin signaling. Thus, Socs2 and Elf5 are key members of the set of prolactin-regulated genes that mediate prolactin-driven mammary development.
David Gallegoortega - One of the best experts on this subject based on the ideXlab platform.
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a mutation in the viral sensor 2 5 oligoadenylate synthetase 2 causes Failure of Lactation
PLOS Genetics, 2017Co-Authors: Samantha R Oakes, David Gallegoortega, Prudence M Stanford, Simon Junankar, Zoya Kikhtyak, Anita Von Korff, Claudio M SergioAbstract:We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum Failure of Lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating Lactation.
Simon Junankar - One of the best experts on this subject based on the ideXlab platform.
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a mutation in the viral sensor 2 5 oligoadenylate synthetase 2 causes Failure of Lactation
PLOS Genetics, 2017Co-Authors: Samantha R Oakes, David Gallegoortega, Prudence M Stanford, Simon Junankar, Zoya Kikhtyak, Anita Von Korff, Claudio M SergioAbstract:We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum Failure of Lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating Lactation.
