|
Allele Symbol Allele Name Allele ID |
Tg(Zp3-cre)93Knw transgene insertion 93, Barbara B Knowles MGI:2176187 |
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| Summary |
37 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal follicular development, showing healthy corpora lutea and preovulatory follicles at 16 weeks of age, normal resumption of meiosis, ovulation, fertilization and fertility, although PI3K-Akt signaling is elevated
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 N |
• female mice exhibit normal ovary morphology and number of primordial follicles
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• in equine chorionic gonadotropin-primed ovaries
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• in prepubertal mice due to detective transition from secondary to antral follicles
• in equine chorionic gonadotropin-primed ovaries
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• in equine chorionic gonadotropin-primed ovaries
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• in equine chorionic gonadotropin-primed ovaries with more activated follicles
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• in equine chorionic gonadotropin-primed ovaries with more activated follicles
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• in equine chorionic gonadotropin-primed ovaries
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• in prepubertal mice due to detective transition from secondary to antral follicles
• in equine chorionic gonadotropin-primed ovaries
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• in equine chorionic gonadotropin-primed ovaries
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• in equine chorionic gonadotropin-primed ovaries with more activated follicles
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• embryos from female mice arrest at the two-cell stage during oocyte-to-embryo transition
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• oocytes exhibit normal oogenesis, in vitro oocyte maturation and in vivo breeding
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 50% of homozygous mice from homozygous females are dead by E15.5 and 90% are dead by E17.5
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• 50% of homozygous mice from homozygous females are dead by E15.5 and 90% are dead by E17.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• oocytes exhibit accelerated anaphase and polar body extrusion compared with wild-type oocytes
• oocytes exhibit defective spindle assembly checkpoint and premature chromosome segregation compared with wild-type oocytes
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• oocytes exhibit accelerated polar body extrusion compared with wild-type oocytes
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• oocytes exhibit defective spindle assembly checkpoint and premature chromosome segregation compared with wild-type oocytes
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• dramatic
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• in female mice
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• 70% of oocytes are aneuploid, with both hyperploidies and hypoploidies, unlike wild-type oocytes
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• oocytes exhibit accelerated anaphase and polar body extrusion compared with wild-type oocytes
• oocytes exhibit defective spindle assembly checkpoint and premature chromosome segregation compared with wild-type oocytes
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• oocytes exhibit accelerated polar body extrusion compared with wild-type oocytes
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• oocytes exhibit defective spindle assembly checkpoint and premature chromosome segregation compared with wild-type oocytes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most fail meiosis I with several phenotypic abnormalities, including abnormal spindle, telophase arrest and abnormal meiosis II oocytes
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• despite normal numbers of oocytes ovulated after hormonal stimulation
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• in vitro, few oocytes are capable of fertilization and the small fraction that are fail to develop past the two-cell stage
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• most fail meiosis I with several phenotypic abnormalities, including abnormal spindle, telophase arrest and abnormal meiosis II oocytes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most fail meiosis I with several phenotypic abnormalities, including abnormal spindle
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• despite normal numbers of oocytes ovulated after hormonal stimulation
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• in vitro, few oocytes are capable of fertilization and the small fraction that are fail to develop past the two-cell stage, telophase arrest and abnormal meiosis II oocytes
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• most fail meiosis I with several phenotypic abnormalities, including abnormal spindle
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
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• oocytes have fewer polar bodies than in wild-type mice
• fewer oocytes at found at the surrounded nucleolus stage than in wild-type oocytes
• more oocytes in the cumulus-oocyte complexes are at the germinal vesicle or abnormal germinal vesicle breakdown stage than in wild-type mice
• following removal of cumulus cells, a higher proportion of oocytes are at the germinal vesicle or abnormal germinal vesicle breakdown stage compared to similarly treated wild-type oocytes
• oocytes exhibit worsening energy status during meiotic maturation unlike wild-type oocytes
• however, oocyte size is normal
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• oocytes have fewer polar bodies than in wild-type mice
• some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies
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• oocytes are atypical of any developmental stage unlike wild-type oocytes that are at metaphase of meiosis I or meiosis II
• some oocytes have highly condensed chromatin and absence of spindle structures unlike wild-type oocytes
• some oocytes exhibit chromatin that is eccentrically located with only occasional evidence of discrete chromosomes or clumps of chromatin unlike in wild-type oocytes
• some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies unlike wild-type oocytes
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• some oocytes have highly condensed chromatin and absence of spindle structures
• some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies
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• oocytes have fewer polar bodies than in wild-type mice
• fewer oocytes at found at the surrounded nucleolus stage than in wild-type oocytes
• more oocytes in the cumulus-oocyte complexes are at the germinal vesicle or abnormal germinal vesicle breakdown stage than in wild-type mice
• following removal of cumulus cells, a higher proportion of oocytes are at the germinal vesicle or abnormal germinal vesicle breakdown stage compared to similarly treated wild-type oocytes
• oocytes exhibit worsening energy status during meiotic maturation unlike wild-type oocytes
• however, oocyte size is normal
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• oocytes have fewer polar bodies than in wild-type mice
• some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies
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• oocytes are atypical of any developmental stage unlike wild-type oocytes that are at metaphase of meiosis I or meiosis II
• some oocytes have highly condensed chromatin and absence of spindle structures unlike wild-type oocytes
• some oocytes exhibit chromatin that is eccentrically located with only occasional evidence of discrete chromosomes or clumps of chromatin unlike in wild-type oocytes
• some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies unlike wild-type oocytes
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• some oocytes have highly condensed chromatin and absence of spindle structures
• some oocytes exhibit chromatin and spindle abnormalities with or without formation of polar bodies
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E8.5 embryos have a sac-like structure composed of 2 layers where the outer layer is reminiscent of the visceral endoderm and the inner layer has characteristics of a pseudostratified epithelium
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• expression analysis indicates failure to gastrulate
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• formation of proper embryonic structures is incomplete
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• absence of embryonic structures at E8.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no embryos survive beyond E10.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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N |
• female mice show no apparent defects in oocyte maturation or fertility
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• nearly all ovulated oocytes exhibit defects in spindle and scattered chromosomes unlike in wild-type oocytes
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• 8 hours post germinal vesicle break-down, oocytes contain abnormal chromosome arrangement and multiple spindles unlike wild-type oocytes
• wild-type germinal vesicles transplanted into oocytes exhibit abnormal meiosis
• however, transplantation of the germinal vesicle into a wild-type oocyte normalizes meiosis
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• 8 hours post germinal vesicle break-down, mutant oocytes contain multiple spindles
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• despite normal numbers of oocytes, female mice are infertile
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• nearly all ovulated oocytes exhibit defects in spindle and scattered chromosomes unlike in wild-type oocytes
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• 8 hours post germinal vesicle break-down, oocytes contain abnormal chromosome arrangement and multiple spindles unlike wild-type oocytes
• wild-type germinal vesicles transplanted into oocytes exhibit abnormal meiosis
• however, transplantation of the germinal vesicle into a wild-type oocyte normalizes meiosis
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• 8 hours post germinal vesicle break-down, mutant oocytes contain multiple spindles
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
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• in oocytes chromosomal length is significantly increased at metaphase I
• significantly blocked in the pro-Mi/MI phase
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• persistent activation of the spindle assembly checkpoint
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• in oocytes chromosomal length is significantly increased at metaphase I
• significantly blocked in the pro-Mi/MI phase
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• persistent activation of the spindle assembly checkpoint
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 46-48 hours after PMSG injection, oocytes exhibit slightly larger diameters than those collected from control females; however, oocyte number, germinal vesicle breakdown, and in vitro maturation to the MII stage are normal
• oocytes express GDF9 proprotein but lack expression of the 17.5 kDa mature GDF9 protein; however, other fertilization related N-glycoproteins (ZP3 and CD9) are expressed normally
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• in vitro, follicles isolated from 12-day-old mice and cultured for 9 days show defective granulosa-oocyte complex (GOC) development with no detectable increase in average follicular volume
• addition of recombinant GDF9 or BMP15 partially restores granulosa cell proliferation and increases follicular volume
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• corpora lutea are rarely detected after PMSG/hCG treatment
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• at 48 hours after PMSG injection, the ovary surface is smooth and follicles appear abnormal
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• after PMSG/hCG treatment, a few preovulatory follicles are found but most of the follicles at the surface of the ovary are immature
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• after PMSG/hCG treatment, the number of antral follicles/section is significantly greater than in control females
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• after PMSG/hCG treatment, the number of cumulus cells that surround an oocyte after germinal vesicle breakdown is significantly decreased and cumulus expansion is impaired
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• after PMSG/hCG treatment, follicular development as arrested at the early antral stage
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• after PMSG/hCG treatment, ovarian weight is significantly lower than in control females, possibly due to defective folliculogenesis
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• after PMSG/hCG treatment, both the total number of ovulated eggs/mouse and number of metaphase II (MII) eggs/mouse are severely reduced
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• when mated with wild-type males, females show a markedly lower pregnancy rate than control females; only 2 litters with 1 pup each are obtained from 16 copulations with 4 females
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• average litter size is 0.1 +/- 0.3 versus 8.4 +/- 2.6 pups in control females
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• after PMSG/hCG treatment, the fertilization rate (number of 2 cell embryos/number of inseminated eggs) is 0% relative to ~70% in control females
• in vitro fertilization efficiency is lower than in controls; however, MII eggs can be fertilized and develop to term after transfer into pseudopregnant females
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• at 46-48 hours after PMSG injection, oocytes exhibit slightly larger diameters than those collected from control females; however, oocyte number, germinal vesicle breakdown, and in vitro maturation to the MII stage are normal
• oocytes express GDF9 proprotein but lack expression of the 17.5 kDa mature GDF9 protein; however, other fertilization related N-glycoproteins (ZP3 and CD9) are expressed normally
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• in vitro, follicles isolated from 12-day-old mice and cultured for 9 days show defective granulosa-oocyte complex (GOC) development with no detectable increase in average follicular volume
• addition of recombinant GDF9 or BMP15 partially restores granulosa cell proliferation and increases follicular volume
|
|
|
• in vitro, follicles isolated from 12-day-old mice and cultured for 9 days show defective granulosa-oocyte complex (GOC) development with no detectable increase in average follicular volume
• addition of recombinant GDF9 or BMP15 partially restores granulosa cell proliferation and increases follicular volume
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• corpora lutea are rarely detected after PMSG/hCG treatment
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• at 48 hours after PMSG injection, the ovary surface is smooth and follicles appear abnormal
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• after PMSG/hCG treatment, a few preovulatory follicles are found but most of the follicles at the surface of the ovary are immature
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|
• after PMSG/hCG treatment, the number of antral follicles/section is significantly greater than in control females
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• after PMSG/hCG treatment, the number of cumulus cells that surround an oocyte after germinal vesicle breakdown is significantly decreased and cumulus expansion is impaired
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• after PMSG/hCG treatment, follicular development as arrested at the early antral stage
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• after PMSG/hCG treatment, ovarian weight is significantly lower than in control females, possibly due to defective folliculogenesis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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N |
• when mated with wild-type males, females exhibit normal fertility with no significant differences in the pregnancy rate or average litter size relative to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• fertility of double mutant females is completely restored from 10-30 weeks of age when mated with wild-type males compared to single conditional homozygous Pdpk1 mutants
• embryos derived from double mutant females mated with wild-type males show normal perimplantation development, indicating rescue of the two-cell arrest and the suppressed embryonic genome activation seen in embryos from single conditional homozygous Pdpk1 mutants
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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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• females are sterile, however follicular development and oocyte maturation are normal
• fertilization is also normal in mutant females, with numbers of two-cell embryos from pregnant females comparable with those from controls
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• 92.5% of two-cell embryos from mutant females mated with wild-type males arrest at the two-cell stage when cultured in vitro compared to 4.2% of wild-type control embryos; heterozygous embryos do not express PDPK1 protein, indicating that this protein is not yet synthesized from the paternal allele in these embryos
• two-cell embryos resulting from mutant female mating to wild-type males exhibit suppression of embryonic genome activation and defective G2-to-M transition of the second mitotic cell cycle
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• blocked at the primary follicle stage
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• blocked at the primary follicle stage
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all oocytes stalled at germinal vesicle stage; do not develop to two-cell stage upon fertilization
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• all oocytes stalled at germinal vesicle stage; do not develop to two-cell stage upon fertilization
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N |
• normal ovary morphology
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• all oocytes stalled at germinal vesicle stage; do not develop to two-cell stage upon fertilization
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• all oocytes stalled at germinal vesicle stage; do not develop to two-cell stage upon fertilization
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• females exhibit normal ovarian histology and follicle counts at 18 days (prepubertal), at 7 weeks, and at 7 months of age, indicating normal folliculogenesis
• when bred with wild type male mice for 6 months, adult females show normal fertility with no significant differences in average litter size or age-associated changes in fertility relative to controls
• fully grown oocytes from hyperstimulated female mice exhibit no changes in oocyte number, germinal vesicle diameter, and nuclear or nucleolar morphology
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• double-oocyte follicles may be derived from a single oocyte, as two nucleus-like structures have been noted in one oocyte
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• 6 of 7 mutant females at diestrus display 1 to 3 follicles containing double oocytes
• double-oocyte follicles are observed at the primary, secondary, and antral stages
• however, ovarian histology is otherwise normal, and no differences in ovary weight or size are observed
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• the expression levels of two oocyte-specific genes, BMP15 and GDF9, are increased >2-fold in mutant ovaries at diestrus (but not at estrus or metestrus) relative to those in control ovaries
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• the diestrus phase of the estrous cycle is significantly prolonged
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• the average length of the estrous cycle is much longer than that of control littermates, as a result of a prolonged diestrus phase
• no differences are observed at the other stages of the estrous cycle
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• female mutants are subfertile, showing a ~50% reduction in the number of litters per month relative to control littermates
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• at day 5 after birth, the number of pups per litter is significantly lower than that of control littermates
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| N |
• at 2-3 months of age, mutant females exhibit:
• normal cicrulating levels of FSH, LH, testosterone and progesterone at proestrus and estrus
• normal estradiol levels at estrus
• normal LH levels at diestrus
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• at diestrus, mutant females display significantly reduced circulating testosterone levels relative control littermates
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• at diestrus, mutant females display significantly reduced circulating estradiol levels relative control littermates
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• at diestrus, mutant females display significantly reduced circulating FSH levels relative control littermates
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• at diestrus, mutant females display significantly reduced circulating progesterone levels relative control littermates
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• 6 of 7 mutant females at diestrus display 1 to 3 follicles containing double oocytes
• double-oocyte follicles are observed at the primary, secondary, and antral stages
• however, ovarian histology is otherwise normal, and no differences in ovary weight or size are observed
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• double-oocyte follicles may be derived from a single oocyte, as two nucleus-like structures have been noted in one oocyte
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• trunk neural crest derivatives are reduced
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• at E10.5, fewer neurons and glia are present in the dorsal root ganglia caudal to the forelimb level
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• neural crest cells undergo more apoptosis than in wild-type mice prior to or shortly after commencing migration to the periphery
• at E10.5, apoptotic cells are increased in the dorsal region of the neural tube caudal to the forelimb level
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• trunk neural crest derivatives are reduced
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• neural crest cells undergo more apoptosis than in wild-type mice prior to or shortly after commencing migration to the periphery
• at E10.5, apoptotic cells are increased in the dorsal region of the neural tube caudal to the forelimb level
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• when bred to wild-type males females produce viable offspring indicating maternal expression is not required for development
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reach the blastocyst stage then collapse around implantation
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• reach the blastocyst stage then collapse around implantation
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• when bred to wild-type males females produce viable offspring indicating maternal expression is not required for development
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a high rate of seizure-induced mortality is observed from 6 weeks through 17 weeks
• Background Sensitivity: with further backcrossing to enrich the C57BL/6J background content, the mortality phenotype is almost eliminated
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• on an obesogenic (high fat,high sugar) diet, higher rate of obesity is observed compared to controls
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• on an obesogenic (high fat,high sugar) diet, higher rate of obesity is observed compared to controls
|
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• mice show enhanced hyperglycemia incidence when fed an obesogenic (high fat,high sugar) diet
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• best grown oocytes from 3-week-old females are smaller in diameter, contain a germinal vesicle (GV) with unclear boundaries and aggregate dark cytoplasmic granules
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• at 8 weeks of age, ovaries are devoid of corpora lutea
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• at 3 weeks of age, ovaries contain fewer growing follicles than those in control females
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• at 8 weeks of age, ovaries are devoid of follicles containing more than two layers of granulosa cells
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• by 5 months of age, only primordial and primary follicles are detected in the ovaries; follicle growth is blocked beyond the primary follicle stage
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• at 3 and 8 weeks of age, ovaries are smaller than in control females
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• 3-week-old females are unresponsive to PMSG treatment
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• after PMSG plus hCG treatment, 3-week-old females ovulate significantly fewer oocytes than superovulated control females
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• when 6-week-old females were mated with wild-type males for 5 months, only one pup was born
|
|
|
• best grown oocytes from 3-week-old females are smaller in diameter, contain a germinal vesicle (GV) with unclear boundaries and aggregate dark cytoplasmic granules
|
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|
• at 8 weeks of age, ovaries are devoid of corpora lutea
|
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• at 3 weeks of age, ovaries contain fewer growing follicles than those in control females
|
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|
• at 8 weeks of age, ovaries are devoid of follicles containing more than two layers of granulosa cells
|
|
|
• by 5 months of age, only primordial and primary follicles are detected in the ovaries; follicle growth is blocked beyond the primary follicle stage
|
|
|
• at 3 and 8 weeks of age, ovaries are smaller than in control females
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• placentas show reduced lectin and CD34 staining indicating changes in vasculature at E9.5 and E12.5
• placentas show differences in vessels organization
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|
• collagen deposition is up-regulated in placentas, with collagen around the yolk sac as in controls but also throughout the labyrinth at E16.5 which is not seen in controls
• increase in fibrin deposition in E16.5 placentas, throughout the decidua basalis and junctional zones
• increase in granulated leukocytes in E12.5 placenta
• marker analysis indicates signs of oxidative stress in the placenta
|
|
• placentas show reduced lectin and CD34 staining indicating changes in vasculature at E9.5 and E12.5
• placentas show differences in vessels organization
|
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• fibrin deposition is increased throughout the decidua basalis
• uterine natural killer cells are increased in the decidual basalis of the placenta throughout gestation
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• uterine natural killer cells are increased in the decidual basalis of the placenta throughout gestation
|
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• uterine natural killer cells are increased in the decidual basalis of the placenta throughout gestation
|
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• increase in granulated leukocytes in E12.5 placenta
|
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• uterine natural killer cells are increased in the decidual basalis of the placenta throughout gestation
|
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• increase in granulated leukocytes in E12.5 placenta
|
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• uterine natural killer cells are increased in the decidual basalis of the placenta throughout gestation
|
|
• fibrin deposition is increased throughout the decidua basalis
• uterine natural killer cells are increased in the decidual basalis of the placenta throughout gestation
|
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• uterine natural killer cells are increased in the decidual basalis of the placenta throughout gestation
|
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• homozygous breeding pairs are slower to achieve pregnancy over time
|
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• reduction in litter size in homozygous females when the embryos carried are homozygous but not when the embryos are heterozygous
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| placental insufficiency | DOID:3891 | J:243365 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• 6-week-old female mice exhibit normal ovary histology and ovary/body weight ratio; folliculogenesis is induced by hormone (eCG) stimulation, suggesting normal oocyte growth
|
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• nearly all oocytes arrest at the germinal vesicle (GV) stage without undergoing nuclear envelope breakdown or completing meiosis
• many poly(A) mRNAs are transformed into uridylated-poly(A) mRNAs which are more stable, resulting in global accumulation of transcripts
• uridylated-poly(A) RNAs are stabilized due to insufficient degradation and tail editing
• insufficient degradation of meiotic repressor transcripts may cause GV arrest
• however, the diameter of GV oocytes and the ratio between surrounded nucleolus (SN) and non-surrounded nucleolus (NSN) oocytes are similar to those of control oocytes
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• transcriptome analysis during meiotic maturation of oocytes showed that the transition from GV to meiosis II (MII) stages is perturbed
• oocytes show a severe and early arrest in transitioning from meiosis I prophase to metaphase
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• female mice are completely infertile
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• nearly all oocytes arrest at the germinal vesicle (GV) stage without undergoing nuclear envelope breakdown or completing meiosis
• many poly(A) mRNAs are transformed into uridylated-poly(A) mRNAs which are more stable, resulting in global accumulation of transcripts
• uridylated-poly(A) RNAs are stabilized due to insufficient degradation and tail editing
• insufficient degradation of meiotic repressor transcripts may cause GV arrest
• however, the diameter of GV oocytes and the ratio between surrounded nucleolus (SN) and non-surrounded nucleolus (NSN) oocytes are similar to those of control oocytes
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• transcriptome analysis during meiotic maturation of oocytes showed that the transition from GV to meiosis II (MII) stages is perturbed
• oocytes show a severe and early arrest in transitioning from meiosis I prophase to metaphase
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• a small cohort of mRNAs are polyadenylated after terminal uridylation in germinal vesicle (GV) oocytes; these uridylated-poly(A) RNAs have shorter poly(A) tails and show reduced translation activity in oocytes
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• a small cohort of mRNAs are polyadenylated after terminal uridylation in germinal vesicle (GV) oocytes; these uridylated-poly(A) RNAs have shorter poly(A) tails and show reduced translation activity in oocytes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are born at normal Mendelian ratios but survive only to P12-P18
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• by P14, mice of both sexes are significantly smaller than wild-type or heterozygous controls
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• by P12-P14, body weight is ~50% that of wild-type or heterozygous controls
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• mice exhibit retarded growth from P10 onwards
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• mice display a stiff walking posture
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• significantly smaller diameter myofibrils in quadriceps muscles
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• increased incidence of centrally located nuclei in quadriceps muscles
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• germinal vesicle oocytes from P21 mice are smaller
• following 12 hours of in vitro culture, about 85.5% of oocytes are arrested at the germinal vesicle stage instead of extruding the first polar body
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• mice show arrested follicle development although some primary follicles are seen at P84
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• mice show arrested follicle development although some primary follicles are seen at P84
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• germinal vesicle oocytes from P21 mice are smaller
• following 12 hours of in vitro culture, about 85.5% of oocytes are arrested at the germinal vesicle stage instead of extruding the first polar body
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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N |
• oocytes exhibit normal oogenesis, in vitro oocyte maturation and in vivo breeding
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• almost all mutants with the paternally inherited deletion survive to adulthood and appear healthy at 18 months
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• at 5 months of age, body lengths of mutant males and females are shorter by around 4 and 3%, respectively, than wild-type mice (differences are statistically significant)
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• when fed a high-fat diet for 4 months from 8 weeks of age, mutants carrying the paternally-inherited deletion gain less weight than wild-type littermates, with the differences more pronounced in males
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• at birth, pups with the paternally-inherited allele are indistinguishable from normal littermates, but beginning at P2, mutants fail to gain weight as effectively as littermates; by 3 weeks, mutant weights are 60% of wild-type male and female weights
• growth rates appear to normalize after weaning, but weight differences persist to maturity in both genders
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| N |
• unlike other mouse models of Prader-Willi syndrome, mutant pups carrying the paternally-inherited deletion show normal milk intake, righting ability, and muscle tone and strenght after birth and during early postnatal period
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• in accelerating rotarod trials at 2 and 5 months of age, mice carrying the paternally-inherited deletion display essentially flat learning curves (little improvement) over a 6-day training period, whereas control animals display significant improvements
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• when provided with a high-fat diet, both wild-type and mutant animals reduce their total food intake, but both mutant males and females have lower food intake during the 'day-time' phase relative to wild-type animals (total energy intake is similar to wild-type, indicating that mutants compensate for reduced 'day-time' intake by increasing intake during dark-phase)
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• at 6 months of age, both males and females carrying the paternally-inherited deletion allele show increases in daily food intake normalized to body weight (22% or 32%, respectively; at 3 months, males show significant hyperphagia relative to wild-type males, but to a lesser degree than at 6 months, while in females carrying the paternally-inherited deletion allele, daily food intake increases do not reach significance
• at 10 months, males and females carrying the paternally-inherited deletion allele display significant hyperphagia with daily food intake increased by 31 and 29% respectively compared to wild-type animals
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• 3-4 month old mice with the paternally-inherited deletion exhibit increased anxiety-relatted behavior in elevated plus-maze tests (more entries into and time spent in closed arms of maze relative to wild-type mice)
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• at P5 and 13, brain weight is only slight decreased (95% and 92%, respectively, of wild-type brain weight)
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| N |
• testis and ovary sizes of mutants carrying the paternally-inherited deletion are proportional to their body size, and histologically normal
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• in mutant females with the paternally-inherited deletion, vaginal opening is delayed by 3.7 days
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| N |
• morphology of pituitary gland in mutants is normal
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• when mice are restricted to 80% of their normal food intake levels, wild-type mice gradually lose weight but animals carrying the paternally-inherited deletion allele are better at maintaining their weight (females are significantly better, but males also show improved weight stability compared to wild-type)
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• when fed a high-fat diet for 4 months from 8 weeks of age, mutants carrying the paternally-inherited deletion gain less weight than wild-type littermates, with the differences more pronounced in males
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• on a high-fat diet, males carrying the paternally-inherited deletion allele have lower resting blood glucose levels and display a smaller peak level after glucose injecion compared to wild-type males
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• when allowed ad libitum food access, adult mice carrying the paternally-inherited deletion allele have ghrelin levels 2.3-fold higher than in wild-type animals
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• animals with paternally-inherited mutant allele have 39% of wild-type level at 4 weeks of age, and 57% of wild-type levels at 8 weeks
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• mice carrying the paternally-inherited deletion allele have significantly rates of oxygen consumption
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• mice carrying the paternally-inherited deletion allele exhibit a higher respiratory exchange ratio than wild-type mice
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• on a normal diet, males carrying the paternally-inherited deletion have similar basal blood glucose levels to wild-type but display significantly increased response to insulin injection; mutant males fed a high-fat diet also display significantly increased insulin sensitivity
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• on high-fat and normal chow diets, animals carrying the paternally-inherited deletion allele display decreased fat storage compared to wild-type animals
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• when fed a high-fat diet for 4 months, mutants carrying the paternally-inherited deletion allele have significantly lower body fat than wild-type animals (mutant males -6.9%, mutant females -7.2% lower than wild-type)
• 5 month-old mutant males on regular chow diet show an insignificant trend (-3.6%) toward decreased body fat content while females show a significant decrease of 4.2% relative to wild-type; 9-month old animals on a regular chow diet significantly lower body fat content (-9% in mutant males, -5% in females)
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• stomachs in animals receiving paternally-inherited mutant allele are significantly smaller than in wild-type littermates; at P5 and 13, stomachs are 67 and 68% the size of wild-type
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• size is strikingly reduced in size upon examination at P5 and 13
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• at P5, liver weight is 72% of wild-type animals, and at p13, liver weight is only 56% of wild-type
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• the Snord116 cluster is imprinted and the maternal copy is silenced during oogenesis; only inheritance of the paternal allele with the Snord116 cluster deletion produces the growth deficiency and polyphagia phenotypes in mice
• when offspring have maternal inheritance of the deleted allele, they are normal in size and show normal lifespans
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Prader-Willi syndrome | DOID:11983 |
OMIM:176270 |
J:131427 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• arrest by E9.0
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• indistinguishable from germ line null mice
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• arrest by E9.0
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• females produce an average of six pups per litter
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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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