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Phenotypes Associated with This Genotype
Genotype
MGI:6854698
Allelic
Composition
Gata4tm1.1Sad/Gata4tm1.1Sad
Amhr2tm3(cre)Bhr/Amhr2+
Genetic
Background
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Amhr2tm3(cre)Bhr mutation (1 available); any Amhr2 mutation (24 available)
Gata4tm1.1Sad mutation (1 available); any Gata4 mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• young adult females show no significant differences in the onset of puberty, length of the estrous cycle, or ovarian follicular development relative to controls (J:173711)
N
• at 2.5 and 6 months of age, males show normal seminal vesicle weights relative to controls (J:169018)
• by 6 months of age, males show marked depletion of germ cells in the later stages of development
• by 6 months of age, multinucleated giant cells, syncytia of degenerating spermatids, are found in the seminiferous tubules
• caspase-3 immunostaining revealed increased germ cell apoptosis at 6 months of age
• males show an age-dependent decline in the % of progressively motile sperm
• males show an age-dependent decline in the % of total motile sperm
• ovaries of eCG plus hCG-treated immature females are significantly smaller than those in similarly treated control ovaries
• however, unstimulated ovaries exhibit normal weight and gross morphology
• by 6 months of age, 6 of 7 (86%) ovaries exhibit very large, non-hemorrhagic cysts versus 0 of 10 (0%) ovaries from control females
• ovarian cysts are lined by a flattened epithelium containing scattered ciliated cells
• ovaries of eCG plus hCG-treated immature females show hemorrhagic follicular cysts on their surface, not observed in similarly treated control ovaries
• at 2.5 and 4 months of age, the seminiferous tubule epithelium shows signs of vacuolar degeneration
• at 4 months, spermatocytes and spermatids are prematurely released from the seminiferous epithelium and sloughed into the epididymis
• by 6 months, tubules show progressive atrophy suggesting marked depletion of germ cells; any remaining germ cells are abnormally positioned within the seminiferous epithelium
• at 2.5 months of age, Sertoli cells exhibit vacuolation and accumulation of large lipid droplets
• Sertoli cell vacuoles are surrounded by membrane and occasionally contain multivesicular body-like structures
• vacuolar membranes are often lined by actin filament bundles with endoplasmic reticulum cisternae located beneath them, suggesting germ cell loss
• number of GATA4-immunoreactive Sertoli cells declines dramatically between 4 and 6 months of age, whereas the number of GATA1-and AR-immunoreactive Sertoli cells remains constant
• at 2.5 and 4 months of age, the seminiferous tubule epithelium shows signs of vacuolar degeneration
• by 6 months, tubules show progressive atrophy at all stages of the seminiferous epithelial cycle as well as dystrophic calcification in severely degenerated tubules
• testes are overtly smaller at 6 months of age
• however, male external genitalia and testicular descent appear normal
• average testis weight is 59% and 41% of control weight at 6 and 8 months of age, respectively
• however, body weight is not significantly altered
• males develop age-dependent testicular atrophy
• ovaries of gonadotropin-stimulated immature females are significantly smaller, release fewer or no oocytes, and exhibit cystic changes and significantly lower mRNA levels of the steroidogenic gene Cyp19a1 than gonadotropin-stimulated control ovaries, with a trend towards reduced Star and Cyp11a1 expression
• however, basal ovarian mRNA levels of Star, Cyp11a1 and Cyp19a1 are normal
• permeability of the blood-testis barrier is significantly increased by 6 months of age
• spermatogenesis is impaired with sloughing of spermatocytes and spermatids into the seminiferous tubule lumen, formation of multinucleated giant cells, and dystrophic calcification
• at 6 months of age, caudal epididymal sperm concentrations are significantly lower than those in control males
• by 6 months of age, the number of elongated spermatids is decreased
• in response to exogenous gonadotropins, immature females show a significant decline in oocyte yield relative to superovulated controls
• however, serum E2 levels of eCG-treated juvenile females are not altered
• one-third of superovulated females tested release no oocytes
• 6 of 18 (33%) 2-mo-old females failed to produce offspring versus only 1 of 20 (5%) of control females
• when housed with males of proven fertility, most 2-mo-old females are sub-fertile
• average litter size produced by females is about half that of control females
• males show an abrupt decline in fertility after the first 5 months of life
• however, males copulate with females at a normal rate

cellular
• by 6 months of age, males show marked depletion of germ cells in the later stages of development
• at 6 months of age, caudal epididymal sperm concentrations are significantly lower than those in control males
• by 6 months of age, the number of elongated spermatids is decreased
• by 6 months of age, multinucleated giant cells, syncytia of degenerating spermatids, are found in the seminiferous tubules
• caspase-3 immunostaining revealed increased germ cell apoptosis at 6 months of age
• males show an age-dependent decline in the % of progressively motile sperm
• males show an age-dependent decline in the % of total motile sperm

endocrine/exocrine glands
• ovaries of eCG plus hCG-treated immature females are significantly smaller than those in similarly treated control ovaries
• however, unstimulated ovaries exhibit normal weight and gross morphology
• by 6 months of age, 6 of 7 (86%) ovaries exhibit very large, non-hemorrhagic cysts versus 0 of 10 (0%) ovaries from control females
• ovarian cysts are lined by a flattened epithelium containing scattered ciliated cells
• ovaries of eCG plus hCG-treated immature females show hemorrhagic follicular cysts on their surface, not observed in similarly treated control ovaries
• at 2.5 and 4 months of age, the seminiferous tubule epithelium shows signs of vacuolar degeneration
• at 4 months, spermatocytes and spermatids are prematurely released from the seminiferous epithelium and sloughed into the epididymis
• by 6 months, tubules show progressive atrophy suggesting marked depletion of germ cells; any remaining germ cells are abnormally positioned within the seminiferous epithelium
• at 2.5 months of age, Sertoli cells exhibit vacuolation and accumulation of large lipid droplets
• Sertoli cell vacuoles are surrounded by membrane and occasionally contain multivesicular body-like structures
• vacuolar membranes are often lined by actin filament bundles with endoplasmic reticulum cisternae located beneath them, suggesting germ cell loss
• number of GATA4-immunoreactive Sertoli cells declines dramatically between 4 and 6 months of age, whereas the number of GATA1-and AR-immunoreactive Sertoli cells remains constant
• at 2.5 and 4 months of age, the seminiferous tubule epithelium shows signs of vacuolar degeneration
• by 6 months, tubules show progressive atrophy at all stages of the seminiferous epithelial cycle as well as dystrophic calcification in severely degenerated tubules
• testes are overtly smaller at 6 months of age
• however, male external genitalia and testicular descent appear normal
• average testis weight is 59% and 41% of control weight at 6 and 8 months of age, respectively
• however, body weight is not significantly altered
• males develop age-dependent testicular atrophy
• ovaries of gonadotropin-stimulated immature females are significantly smaller, release fewer or no oocytes, and exhibit cystic changes and significantly lower mRNA levels of the steroidogenic gene Cyp19a1 than gonadotropin-stimulated control ovaries, with a trend towards reduced Star and Cyp11a1 expression
• however, basal ovarian mRNA levels of Star, Cyp11a1 and Cyp19a1 are normal
• permeability of the blood-testis barrier is significantly increased by 6 months of age

homeostasis/metabolism
N
• at 5-8 months of age, males show normal circulating levels of FSH and inhibin B relative to controls
• serum anti-Mullerian hormone (AMH) levels are normal in 2.5-mo-old females but significantly lower than in female controls at 6 months of age, indicating impaired granulosa cell function

growth/size/body
• by 6 months of age, 6 of 7 (86%) ovaries exhibit very large, non-hemorrhagic cysts versus 0 of 10 (0%) ovaries from control females
• ovarian cysts are lined by a flattened epithelium containing scattered ciliated cells
• ovaries of eCG plus hCG-treated immature females show hemorrhagic follicular cysts on their surface, not observed in similarly treated 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
01/06/2026
MGI 6.24
The Jackson Laboratory