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Allele Symbol Allele Name Allele ID |
Yy1tm1Yshi targeted mutation 1, Yang Shi MGI:2445451 |
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| Summary |
5 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• death before E8.5
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• implantation occurs, but embryos fail to differentiate thereafter
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• incomplete penetrance, seen in ~25% of mixed strain heterozygotes
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• incomplete penetrance, seen in ~25% of mixed strain heterozygotes
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• incomplete penetrance, seen in ~25% of mixed strain heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• about 25% of mice die between E13.5 and E14.5 and another 25% die between E16.5 and E19.5
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• all mice that survive until birth die within 48 hours
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• pups isolated at E19.5 fail to inflate their lungs despite visible breathing efforts
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• MEFs proliferate slower and produce smaller colonies
• Cre mediated recombination of the floxed allele produced a decrease in colony number and size and stopped proliferation by blocking cytokinesis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E7.0, Nodal is ectopically expressed throughout the posterior half of the epiblast, instead of being confined to the anterior streak as in control embryos; by E7.5, Nodal is expressed throughout the posterior epiblast and streak derivates instead of being confined to the node as in control embryos
• at E7.0, Foxa2 is properly localized to the anterior visceral endoderm (AVE) but is aberrantly expressed throughout distally located streak derived cells; by E7.5, Foxa2 is inappropriately expressed in a large swath of distally located streak derived cells
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• embryonic to extraembryonic signaling is impaired, resulting in aberrant morphogenetic movements during gastrulation
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• definitive endoderm (DE) is specified but fails to properly integrate into the outer layer; Hex-positive DE cells fail to intercalate into the visceral endoderm (VE)
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• although anterior neuroectoderm is specified, mesoderm production is severely restricted
• analysis of nascent mesoderm markers shows that Lefty2 and Fgf4 are completely absent at E7.5 while Snail and Fgf8 expression is markedly reduced with weak areas of expression confined to the distal-most mesoderm at E7.0
• pharmacological inhibition of Nodal signaling with SB505124 partially restores mesoderm production: in culture, SB505124-treated embryos show increased mesodermal-like streak derivatives, a slight increase in T expression, a marked increase in mesodermal marker transcripts (Tbx6, Twist1 and Snail), a reduction of Nodal, Cer1, Eomes and Foxa2, but no effect on the loss of Lefty2 or Fgf4, suggesting that both Nodal-dependent and Nodal-independent events contribute to the gastrulation defects
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• although expression of both Cer1 and Hex is properly localized to the anterior visceral endoderm (AVE) at E7.0, expression of both genes is significantly reduced, suggesting impaired embryonic (epiblast) to extraembryonic (AVE) signaling
• at E7.0, the Otx2 expression domain is reduced and fails to become anteriorly restricted; by E7.5 Otx2 is confined to a small population of distal epiblast cells
• however, Oct4 and Sox2 expression is normal at E7.0 and E7.5, indicating that neural specification is initiated
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• embryos are smaller than controls at E6.5 and E7.0
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• no head folds are present at E7.5
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• no morphological notochord is present at E7.5
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• no morphological embryonic node is present at E7.5
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• although embryos initiate gastrulation, both primitive streak (PS) formation and ingression through the streak is severely impaired
• at E7.5, a PS is present but shows a distinct accumulation of cells proximal to the streak, suggesting defects in epithelial to mesenchymal transition (EMT)
• PS derivatives fail to repress E-cadherin (CDH1) and migrate properly, unlike in wild-type embryos
• PS formation is compromised, as indicated by reduced brachyury (T) expression, loss of the mesoderm markers Lefty2, Snail and Fgf8, and excess extraembryonic and embryonic Bmp4 and Eomes
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• at E7.0, the expression domain of brachyury (T) is decreased relative to controls; by E7.5, T expression has failed to extend distally, consistent with a drastic reduction in overall streak size
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• E7.5 embryos exhibit an abnormal extraembryonic region
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• Eomes and Bmp4 are overexpressed in the distal extraembryonic ectoderm at E7.0 and E7.5, respectively, instead of being downregulated as in control embryos
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• at E7.5, a thickened HNF4A-positive visceral endoderm (VE) surrounds both the embryonic and extraembryonic tissues of the conceptus, unlike in control embryos where VE surrounds only the extraembryonic tissues, indicating an absence of the DE-mediated dispersal of VE
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• embryos are smaller than controls at E6.5 and E7.0
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• oocytes rarely grow larger than 50 um in diameter, indicating arrested oocyte growth
• oocyte-specific expression of Gdf9 and Bmp15 is nearly undetectable
• oocytes exhibit altered levels of several oocyte-specific factors, including Pou5f1, Figla, Lhx8, Oosp1, and Sohlh2
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• secondary follicles often contain a degenerating oocyte
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• no mature follicles are observed
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• percent of follicles in the primary stage is significantly higher than in controls (83% versus 20%)
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• no multilayered, antral follicles or Graafian follicles are observed
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• ovarian follicle maturation is halted; no post-secondary follicles are observed
• however, no differences are observed in the number of primordial follicles
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• some secondary follicles exhibit an irregular/incomplete second layer of granulosa cells and often contain a degenerating oocyte
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• percent of follicles in the secondary stage is significantly lower than in controls (17% versus 45%)
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• adult females show a ~30% reduction in ovary size relative to control females
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• in whole ovaries, mRNA levels of Gdf9 and Bmp15 are nearly undetectable, whereas mRNA levels of Bmp6, Kit, and Kitl are significantly increased relative to control ovaries
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• although vaginal cytology indicates estrus stage changes, no regular cycle or periodicity is observed during a 3-wk test period indicating failure of estrus cycling
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• when placed individually with wild-type males, 6-wk-old females never appeared pregnant or produced offspring
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• serum inhibin-A levels are decreased or undetectable in all females examined, regardless of staging by vaginal cytology
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• serum FSH levels are dramatically increased in females, regardless of staging by vaginal cytology
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• vaginal plugs are infrequently detected during a 5-mo breeding trial
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• oocytes rarely grow larger than 50 um in diameter, indicating arrested oocyte growth
• oocyte-specific expression of Gdf9 and Bmp15 is nearly undetectable
• oocytes exhibit altered levels of several oocyte-specific factors, including Pou5f1, Figla, Lhx8, Oosp1, and Sohlh2
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• secondary follicles often contain a degenerating oocyte
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• no mature follicles are observed
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• percent of follicles in the primary stage is significantly higher than in controls (83% versus 20%)
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• no multilayered, antral follicles or Graafian follicles are observed
|
|
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• ovarian follicle maturation is halted; no post-secondary follicles are observed
• however, no differences are observed in the number of primordial follicles
|
|
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• some secondary follicles exhibit an irregular/incomplete second layer of granulosa cells and often contain a degenerating oocyte
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• percent of follicles in the secondary stage is significantly lower than in controls (17% versus 45%)
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• adult females show a ~30% reduction in ovary size relative to control females
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• in whole ovaries, mRNA levels of Gdf9 and Bmp15 are nearly undetectable, whereas mRNA levels of Bmp6, Kit, and Kitl are significantly increased relative to control ovaries
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 07/05/2024 MGI 6.24 |
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