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Ovarian Kaleidoscope Database (OKdb)



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Hsueh lab


since 01/2001:


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DNA Microarrays
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General Comment SOCS (suppressor of cytokine signaling) proteins, also known as SSI (STAT-induced STAT inhibitor) proteins, have been shown to be negative regulators of cytokine receptor signaling via the Janus kinase signal transducer and activation of transcription (STAT; see OMIM 600555) pathway (the JAK/STAT pathway).

General function Intracellular signaling cascade, Cell death/survival, Anti-apoptotic
Cellular localization Cytoplasmic
Ovarian function Follicle development, Luteinization
Comment Freiman RN, et al 2001 reported the requirement of Tissue-Selective TBP-Associated Factor TAFII105 in Ovarian Development. Transcription factor TFIID, composed of TBP and TAF(II) subunits, is a central component of the RNA polymerase II machinery. Female mice lacking TAF(II)105 are viable but infertile because of a defect in folliculogenesis correlating with restricted expression of TAF(II)105 in the granulosa cells of the ovarian follicle. Gene expression profiling has uncovered a 3.4 fold decrease in the expression of SOCS-2 .
Expression regulated by LH
Comment Changes in mouse granulosa cell gene expression during early luteinization. McRae RS et al. Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.
Ovarian localization Granulosa, Luteal cells
Comment Tam SP et al 2001 reported the tissue-specific induction of SOCS gene expression by PRL. They report the expression of mRNA and protein for members of the SOCS/CIS/JAB family of cytokine signaling inhibitors is increased by PRL administration in ovary and adrenal gland of the lactating rat deprived of circulating PRL and pups for 24 h but not in mammary gland. Moreover, suckling increases SOCS mRNA in the ovary but not in the mammary gland of pup-deprived rats. In reporter assays, SOCS-1, SOCS-3, and CIS, but not SOCS-2, are able to inhibit transactivation of the STAT 5-responsive beta -lactoglobulin promoter in transient transfection assays. Moreover, suckling results in loss of ovarian and adrenal responsiveness to PRL administered 2 h after commencement of suckling, as determined by STAT 5 gel shift assay. Immunohistochemistry was used to localize the cellular sites of SOCS-3 and CIS protein expression in the ovary and adrenal gland. It was proposed that induced SOCS-1, SOCS-3, and CIS are actively involved in the cellular inhibitory feedback response to physiological PRL surges in the corpus luteum and adrenal cortex during lactation, but after pup withdrawal, the mammary gland is rendered unresponsive to PRL by increased levels of SOCS-3.
Follicle stages Corpus luteum
Comment Maximal expression of Suppressors of Cytokine Signalling (SOCS) in the rat ovary occurs in late pregnancy. Anderson S et al. Maintenance of the rodent corpus luteum during pregnancy requires prolactin-receptor (PRL-R) signal transduction via STAT5. At the end of pregnancy prostaglandin F2alpha (PGF2alpha) induces luteal regression through many mechanisms, including down-regulation of PRL-R signaling. We have previously shown that a PGF2alpha analog upregulates Suppressors of Cytokine Signaling (SOCS) proteins in the corpus luteum of Day 19 pregnant rats leading to reduced STAT5 signaling. Here we examined endogenous SOCS expression and STAT5 signaling in the rat ovary during normal pregnancy and luteolysis. The mRNA expression of SOCS1, SOCS2 and SOCS3 and related Cytokine-inducible SH2-containing protein (CIS) was low in early pregnancy (Day 7), but significantly increased at mid-pregnancy (Days 10 and 13) associated with increased endogenous tyrosine phosphorylation (TyrP) of STAT5. In support of the notion that these changes are due to increasing placental lactogen levels at this time, we found that treatment with exogenous prolactin on Day 7 increased TyrP of STAT5 and induced SOCS mRNA expression, except SOCS3. After mid-pregnancy, further significant increases in SOCS3 and CIS mRNA expression were observed. Such changes in mRNA expression correlated with protein levels, with protein levels of both SOCS3 and CIS being maximal in late pregnancy (Days 19 to 21). In addition a significant reduction in TyrP of STAT5 was first observed on Day 20, with a further substantial decrease on Day 21. Therefore these results are consistent with the hypothesis that increased SOCS expression in the rat ovary during late pregnancy reduces STAT5 signaling which may be important in PGF2alpha-induced luteolysis.
Mutations 1 mutations

Species: mouse
Mutation name: None
type: null mutation
fertility: fertile
Comment: Metcalf et al. (2000) generated mice deficient in SOCS2 by targeted disruption. SOCS2-deficient mice were indistinguishable from their littermates until weaning at 3 weeks of age, but subsequently grew more rapidly. SOCS2 -/- adult males were on average 40% heavier than wildtype littermates. Adult SOCS2 +/- males exhibited an intermediate body weight. Increased growth was also significant but less marked in female SOCS2 -/- mice. Adult SOCS2 -/- females typically attained the weight of wildtype male mice, but heterozygous SOCS2 females were not significantly heavier than sex-matched wildtype littermates. Neither male nor female SOCS2 -/- mice accumulated significantly more fatty tissue than wildtype mice. Rather, increased body weight in these mice resulted from an increase in the weight of most visceral organ

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created: Oct. 1, 2001, 3:42 p.m. by: hsueh   email:
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last update: June 10, 2009, 5:43 a.m. by: hsueh    email:

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