Phenotypes Associated with This Genotype

Genotype
MGI:3512787

• Allelic Composition: Wt1^tm1Vih/Wt1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

reproductive system

impaired granulosa cell differentiation ( J:204518 )

♀ • at 3 weeks of age, 3beta-HSD protein is detected not only in the interstitium (as in control ovaries) but also in the granulosa cells of small follicles (unlike in control ovaries); also, mRNA expression of LHR, aromatase and FSHR is increased whereas mRNA expression of Amh is reduced, suggesting premature differentiation of granulosa cells

abnormal granulosa cell morphology ( J:204518 )

♀ • at 3 weeks of age, many developing follicles show asymmetric granulosa cells or no granulosa cells with cuboidal morphology

impaired ovarian folliculogenesis ( J:204518 )

♀ • at 1 week of age, the total number of developing follicles with multiple layers of granulosa cells is significantly lower than that in control ovaries (~44 versus ~205, respectively)

♀ • at 3 weeks of age, the number of developing follicles is significantly reduced and many aberrant follicles with undifferentiated squamous granulosa cells are observed

♀ • when follicles with 2-3 layers of granulosa cells are obtained from 2-week-old ovaries and cultured in vitro, only ~11% of follicles develop to the pre-ovulatory stage and most follicles are relatively small or exhibit detached oocytes after 11 days in culture, whereas ~80% of control follicles develop to the preovulatory stage with a notable antrum

♀ • aberrant follicle development is likely due to premature differentiation and abnormal cell polarity establishment of granulosa cells

♀ • however, granulosa cell proliferation is normal, as shown by Ki67 staining

abnormal primary ovarian follicle morphology ( J:204518 )

♀ • at 1 week of age, many primary follicles with asymmetric and disorganized granulosa cells are observed

small ovary ( J:204518 )

♀ • ovary size is dramatically reduced at 3 weeks of age

decreased ovulation rate ( J:204518 )

♀ • ovulation rate of females is severely reduced with an average of only 2 oocytes obtained by natural ovulation versus 8 oocytes in control females

decreased superovulation rate ( J:204518 )

♀ • after hormone stimulation, 3-week-old females release less than 5 oocytes versus ~64 oocytes released from control females

reduced female fertility ( J:204518 )

♀ • only ~15% of plugged females become pregnant after mating with wild-type males versus 88.2% of control females

cellular

impaired granulosa cell differentiation ( J:204518 )

♀ • at 3 weeks of age, 3beta-HSD protein is detected not only in the interstitium (as in control ovaries) but also in the granulosa cells of small follicles (unlike in control ovaries); also, mRNA expression of LHR, aromatase and FSHR is increased whereas mRNA expression of Amh is reduced, suggesting premature differentiation of granulosa cells

endocrine/exocrine glands

impaired granulosa cell differentiation ( J:204518 )

♀ • at 3 weeks of age, 3beta-HSD protein is detected not only in the interstitium (as in control ovaries) but also in the granulosa cells of small follicles (unlike in control ovaries); also, mRNA expression of LHR, aromatase and FSHR is increased whereas mRNA expression of Amh is reduced, suggesting premature differentiation of granulosa cells

abnormal granulosa cell morphology ( J:204518 )

♀ • at 3 weeks of age, many developing follicles show asymmetric granulosa cells or no granulosa cells with cuboidal morphology

impaired ovarian folliculogenesis ( J:204518 )

♀ • at 1 week of age, the total number of developing follicles with multiple layers of granulosa cells is significantly lower than that in control ovaries (~44 versus ~205, respectively)

♀ • at 3 weeks of age, the number of developing follicles is significantly reduced and many aberrant follicles with undifferentiated squamous granulosa cells are observed

♀ • when follicles with 2-3 layers of granulosa cells are obtained from 2-week-old ovaries and cultured in vitro, only ~11% of follicles develop to the pre-ovulatory stage and most follicles are relatively small or exhibit detached oocytes after 11 days in culture, whereas ~80% of control follicles develop to the preovulatory stage with a notable antrum

♀ • aberrant follicle development is likely due to premature differentiation and abnormal cell polarity establishment of granulosa cells

♀ • however, granulosa cell proliferation is normal, as shown by Ki67 staining

abnormal primary ovarian follicle morphology ( J:204518 )

♀ • at 1 week of age, many primary follicles with asymmetric and disorganized granulosa cells are observed

small ovary ( J:204518 )

♀ • ovary size is dramatically reduced at 3 weeks of age

renal/urinary system

renal/urinary system phenotype ( J:94225 )

N • no proteinuria or glomerulosclerosis detected unlike on a mixed 129S7/SvEvBrd, C57BL/6, and MF1 background