reproductive system
• fewer oocytes are detected at P1 and P3
|
• no oocytes are observed at P10, suggesting premature ovarian failure
|
• no round or elongated spermatids are observed in the seminiferous tubules at P42
• ratios of WT1+ Sertoli cells to PLZF+ cells (undifferentiated and differentiating spermatogonia) are similar to those in wild-type testes
|
azoospermia
(
J:344887
)
• at P42, epididymides are consistently devoid of mature spermatozoa
|
• incomplete synapsis is observed in testes sections stained for SYCP1 and SYCP3 and in spermatocytes stained for HORMAD1 (an unsynapsed chromosome marker) and SYCP3
|
• at P1, meiotic primordial germ cells (PGCs) show defects in RAD51 and DMC1 removal; PGCs are RAD51- and DMC1-positive throughout the nucleus, whereas wild-type PGCs are at diplotene stage with no or weak RAD51/DMC1 signals
|
• persistent foci of RAD51 and DMC1 foci (markers of early recombination intermediates in meiosis) are found in spermatocytes at the zygotene-like stage; extensive RAD51 and DMC1 foci are detected on both unsynapsed and synapsed regions
• number of RAD51 foci only shows a 13% decrease while number of DMC1 foci exhibits just a 23% decrease during the early-zygotene to zygotene-like transition, indicating defects in RAD51/DMC1 removal during meiotic recombination
• at P42, intensity of RAD51 and DMC1 signals is stronger than in wild-type testes
• RAD51 and DMC1 foci frequently co-localize with TEX11 and SHOC1; in zygotene-like spermatocytes, co-localization frequencies for RAD51/TEX11 and DMC1/SHOC1 pairs are 42% and 37%, respectively
• fewer MSH4 foci are observed in zygotene-like spermatocytes; 87% of MSH4 foci co-localize with DMC1, while MLH1 foci (a marker of late recombination intermediates) are almost absent, suggesting that defective RAD51/DMC1 removal impairs meiotic homologous recombination
|
• even in the most advanced zygonema-like spermatocytes, SYCP1 stretches do not extend to the full length, remaining short and sometimes increasing in numbers
|
• at P42, testes show a massive number of TUNEL+ cells
|
small ovary
(
J:344887
)
• ovaries are significantly smaller than in wild-type controls
|
• after P25, ovaries are almost undetectable and hard to be dissected from the oviducts
|
• at P42, seminiferous tubules are smaller with large cavities and no round or elongated spermatids are observed
|
small testis
(
J:344887
)
• at P42, testes are significantly smaller than in wild-type controls
|
• at P42, testis weight is 21.05 +/- 0.80 mg versus 72.48 +/- 3.01 mg in wild-type controls
|
• spermatogenesis is arrested at meiotic prophase I
|
• spermatocytes show impaired meiotic prophase I progression; at P21, pachynema and diplonema with gammaH2AX signals (marking double strand breaks) on sex bodies are not found, unlike in wild-type testes
• ~60% of spermatocytes are arrested at a zygotene-like stage that is similar to the late-zygonema in wild-type testes
|
infertility
(
J:344887
)
• both male and female mice are infertile
|
cellular
• fewer oocytes are detected at P1 and P3
|
• no oocytes are observed at P10, suggesting premature ovarian failure
|
• no round or elongated spermatids are observed in the seminiferous tubules at P42
• ratios of WT1+ Sertoli cells to PLZF+ cells (undifferentiated and differentiating spermatogonia) are similar to those in wild-type testes
|
azoospermia
(
J:344887
)
• at P42, epididymides are consistently devoid of mature spermatozoa
|
• incomplete synapsis is observed in testes sections stained for SYCP1 and SYCP3 and in spermatocytes stained for HORMAD1 (an unsynapsed chromosome marker) and SYCP3
|
• at P1, meiotic primordial germ cells (PGCs) show defects in RAD51 and DMC1 removal; PGCs are RAD51- and DMC1-positive throughout the nucleus, whereas wild-type PGCs are at diplotene stage with no or weak RAD51/DMC1 signals
|
• persistent foci of RAD51 and DMC1 foci (markers of early recombination intermediates in meiosis) are found in spermatocytes at the zygotene-like stage; extensive RAD51 and DMC1 foci are detected on both unsynapsed and synapsed regions
• number of RAD51 foci only shows a 13% decrease while number of DMC1 foci exhibits just a 23% decrease during the early-zygotene to zygotene-like transition, indicating defects in RAD51/DMC1 removal during meiotic recombination
• at P42, intensity of RAD51 and DMC1 signals is stronger than in wild-type testes
• RAD51 and DMC1 foci frequently co-localize with TEX11 and SHOC1; in zygotene-like spermatocytes, co-localization frequencies for RAD51/TEX11 and DMC1/SHOC1 pairs are 42% and 37%, respectively
• fewer MSH4 foci are observed in zygotene-like spermatocytes; 87% of MSH4 foci co-localize with DMC1, while MLH1 foci (a marker of late recombination intermediates) are almost absent, suggesting that defective RAD51/DMC1 removal impairs meiotic homologous recombination
|
• spermatocytes show impaired meiotic prophase I progression; at P21, pachynema and diplonema with gammaH2AX signals (marking double strand breaks) on sex bodies are not found, unlike in wild-type testes
• ~60% of spermatocytes are arrested at a zygotene-like stage that is similar to the late-zygonema in wild-type testes
|
• even in the most advanced zygonema-like spermatocytes, SYCP1 stretches do not extend to the full length, remaining short and sometimes increasing in numbers
|
• at P42, testes show a massive number of TUNEL+ cells
|
endocrine/exocrine glands
small ovary
(
J:344887
)
• ovaries are significantly smaller than in wild-type controls
|
• after P25, ovaries are almost undetectable and hard to be dissected from the oviducts
|
• at P42, seminiferous tubules are smaller with large cavities and no round or elongated spermatids are observed
|
small testis
(
J:344887
)
• at P42, testes are significantly smaller than in wild-type controls
|
• at P42, testis weight is 21.05 +/- 0.80 mg versus 72.48 +/- 3.01 mg in wild-type controls
|
mortality/aging