Analysis Tools
mortality/aging
| N |
• viable and present at the expected Mendelian ratio at P1
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Allele Symbol Allele Name Allele ID |
Gata4tm1.1Sad targeted mutation 1.1, Stephen A Duncan MGI:3778685 |
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| Summary |
15 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• viable and present at the expected Mendelian ratio at P1
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 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)
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 N |
• at 2.5 and 6 months of age, males show normal seminal vesicle weights relative to controls
(J:169018)
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• by 6 months of age, males show marked depletion of germ cells in the later stages of development
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• by 6 months of age, multinucleated giant cells, syncytia of degenerating spermatids, are found in the seminiferous tubules
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• caspase-3 immunostaining revealed increased germ cell apoptosis at 6 months of age
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• males show an age-dependent decline in the % of progressively motile sperm
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• males show an age-dependent decline in the % of total motile sperm
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• 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
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• 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
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• 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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• 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
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• 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
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• 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
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• testes are overtly smaller at 6 months of age
• however, male external genitalia and testicular descent appear normal
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• 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
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• males develop age-dependent testicular atrophy
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• 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
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• permeability of the blood-testis barrier is significantly increased by 6 months of age
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• spermatogenesis is impaired with sloughing of spermatocytes and spermatids into the seminiferous tubule lumen, formation of multinucleated giant cells, and dystrophic calcification
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• at 6 months of age, caudal epididymal sperm concentrations are significantly lower than those in control males
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• by 6 months of age, the number of elongated spermatids is decreased
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• 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
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• one-third of superovulated females tested release no oocytes
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• 6 of 18 (33%) 2-mo-old females failed to produce offspring versus only 1 of 20 (5%) of control females
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• when housed with males of proven fertility, most 2-mo-old females are sub-fertile
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• average litter size produced by females is about half that of control females
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• males show an abrupt decline in fertility after the first 5 months of life
• however, males copulate with females at a normal rate
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• by 6 months of age, the number of elongated spermatids is decreased
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• by 6 months of age, males show marked depletion of germ cells in the later stages of development
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• at 6 months of age, caudal epididymal sperm concentrations are significantly lower than those in control males
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• by 6 months of age, multinucleated giant cells, syncytia of degenerating spermatids, are found in the seminiferous tubules
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• caspase-3 immunostaining revealed increased germ cell apoptosis at 6 months of age
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• males show an age-dependent decline in the % of progressively motile sperm
|
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• 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
|
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• 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
|
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• 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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• 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
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• 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
|
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• testes are overtly smaller at 6 months of age
• however, male external genitalia and testicular descent appear normal
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• 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
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• males develop age-dependent testicular atrophy
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• 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
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• permeability of the blood-testis barrier is significantly increased by 6 months of age
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N |
• at 5-8 months of age, males show normal circulating levels of FSH and inhibin B relative to controls
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• 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
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• 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
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• 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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• VSD in all newborns, majority with atrio-ventricular septal defects (AVSDs)
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• mice born at below Mendelian ratios
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• 63% newborns die by age P1
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| atrioventricular septal defect | DOID:0050651 |
OMIM:606215 OMIM:614430 OMIM:614474 |
J:322763 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• normal Mendelian ratios are observed through E14.5, but all mutants are necrotic by E15.5; no living animals are present at weaning
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• at E13.5, hearts display some coronary plexus formation near the base with significantly vessel decreased spreading towards the apex
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• numbers of sub-epicardial endothelial cells are decreased by <90% at E13.5 compared to wild-type
• numbers of epicardial cells are not different from wild type at E13.5
• 3-fold fewer inner-myocardial endothelial cells are detected in mutant hearts at E13.5
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• one third of E13.5 hearts display myocardial thinning (<2 SD from mean of wild-type)
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• mutants show decreased ventricular thickness compared to wild-type
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• at E13.5, myocardial proliferation is decreased compared to wild-type, contribution to the observed myocardial thinning
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• hind limb polydactyly is observed in E14.5 embryos
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• at E13.5, myocardial proliferation is decreased compared to wild-type, contribution to the observed myocardial thinning
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• one third of E13.5 hearts display myocardial thinning (<2 SD from mean of wild-type)
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• at E13.5, myocardial proliferation is decreased compared to wild-type, contribution to the observed myocardial thinning
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants are viable through E15.5, with a small number recovered at weaning
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• a statistically significant decrease in sub-epicardicardial endothelial cells is observed at E13.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants are viable through E15.5, with a small number recovered at weaning
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• a statistically significant decrease in sub-epicardicardial endothelial cells is observed at E13.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not develop diaphragmatic hernias
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| N |
• mice do not exhibit lung defects
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mice die within a few hours of birth
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• mice exhibit a defect in the number and localization of muscle progenitors at E12.5
• at E14.5, differentiating myofibers are aberrant and myofibers and Pax7+ and MyoD+ muscle progenitors are absent in localized regions
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• the number of muscle progenitors is reduced by increased cell death and decreased proliferation
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• 100% of mice develop multiple hernias throughout the diaphragm
• overt herniation of liver through the diaphragm first occurs at E16.5
• size and location of hernias vary, with 68% forming in the dorsal lateral diaphragm (Bochdalek hernias) and 32% developing in the ventral diaphragm (Morgagni hernias)
• hernias occur only in muscle-associated regions and not in the central tendon
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• increase in the number of apoptotic cells in E12.5 embryos, many of which are present in regions that are abnormally devoid or muscle and consistently give rise to hernias
• decrease in the number of proliferative muscle progenitor cells in E12.5 embryos
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• mice exhibit low oxygen blood saturation
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• defects in the lung lobar structure
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• up to a 34% reduction in lung volume of lobes adjacent to hernias
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| congenital diaphragmatic hernia | DOID:3827 |
OMIM:142340 OMIM:222400 OMIM:610187 |
J:231793 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 30% of cells having Gata4 expression are larger than Gata4-deficient cells in the heart
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• heart displays dilation, but this is less prominent than if deletion is produced by Tg(Myh7-cre)1Jmk
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• significant reduction of fractional shortening is observed at 24 weeks
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• 30% of cells having Gata4 expression are larger than Gata4-deficient cells in the heart
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• significant reduction of fractional shortening is observed at 24 weeks
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• following transverse aortic constriction (TAC), severe pulmonary edema is observed
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• following transverse aortic constriction (TAC), severe pulmonary edema is observed
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• animals die between E12.5 and E15.5
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• uniform reduction in ventricular wall thickness is observed in embryos
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• higher levels of apoptosis (TUNEL) are observed compared to Myh6-cre; Gata4-conditional mutants
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• higher levels of apoptosis (TUNEL) are observed compared to Myh6-cre; Gata4-conditional mutants
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• higher levels of apoptosis (TUNEL) are observed compared to Myh6-cre; Gata4-conditional mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by 40 weeks of age, around 25% of mutants have died
• when transverse aortic constriction (TAC) is performed, around 10% mutants and controls die, but in contrast to controls, mutants exhibit mortality in the postsurgical period
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• following 4 weeks of TAC, significant reduction in cardiomyocyte area is observed compared to control cells
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• following 4 weeks of TAC, hypertrophic response is 40-50% of that measured in controls after TAC
• swimming-induced cardiac hypertrophy is significantly less than in wild-type controls
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• following 4 weeks of TAC, ventricular wall thickness shows attenuated growth (hypertrophy) compared to controls
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• TAC performed at 8 weeks of age rapidly and progressively induces decompensation and dilation in mutants but not in controls when examined at 1, 2, 3, and 4 weeks following surgery
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• mutants show significant increases in left ventricular end-systolic and -diastolic volumes indicating ventricular dilation
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• significant reduction in fractional shortening is observed at 12 weeks, and progressively worsens to 24 weeks of age
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• baseline apoptosis in cardiomyocytes measured by TUNEL staining is significantly increased relative to controls at 12 and 20 weeks of age
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• following 4 weeks of TAC, significant reduction in cardiomyocyte area is observed compared to control cells
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• significant reduction in fractional shortening is observed at 12 weeks, and progressively worsens to 24 weeks of age
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• baseline apoptosis in cardiomyocytes measured by TUNEL staining is significantly increased relative to controls at 12 and 20 weeks of age
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• following TAC, mice show severe pulmonary edema whereas control animals do not develop edema
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• following TAC, mice show severe pulmonary edema whereas control animals do not develop edema
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• baseline apoptosis in cardiomyocytes measured by TUNEL staining is significantly increased relative to controls at 12 and 20 weeks of age
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• following 4 weeks of TAC, hypertrophic response is 40-50% of that measured in controls after TAC
• swimming-induced cardiac hypertrophy is significantly less than in wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• despite the absence of Gata4 in the endocardium, trabeculae were found in E10.5 embryos
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hypertrophy is markedly attenuated compared to mutant mice not expressing cre
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• about a 30% increase in ventricular weight compared to mutant mice not carrying the transgene
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• about a 30% increase in ventricular weight compared to mutant mice not carrying the transgene
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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 04/23/2024 MGI 6.23 |
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