Analysis Tools
mortality/aging
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• seen in 46 of 170 heterozygotes; time not specified
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cellular
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• TUNEL analysis indicated a significant increase of granulosa cell apoptosis in the antral follicles of mutant ovaries
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• mutant granulosa cells exhibit a reduced proliferation rate relative to wild-type cells
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growth/size/body
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• have small, white upper and lower incisors that are prone to breakage, instead of the normal yellow, enamel covered teeth
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• very thin, porous enamel layer that is almost non-existent in some areas
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• lower incisors are prone to breakage
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limbs/digits/tail
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• digit 1 (pollex) on the forelimb consists of a thickened, malformed bone
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• the middle phalange on the last digit of both the forelimb and hindlimb is absent
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syndactyly
(
J:101733
)
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• variable fusion of digits 2, 3, and 4 on all limbs; fusion of soft tissue but not bone
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skeleton
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• exhibit skull shape alterations, including, depression across the bridge of the nose and eye socket, and an outward displacement of the frontal and occipital bones
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• have small, white upper and lower incisors that are prone to breakage, instead of the normal yellow, enamel covered teeth
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• very thin, porous enamel layer that is almost non-existent in some areas
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• lower incisors are prone to breakage
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• the middle phalange on the last digit of both the forelimb and hindlimb is absent
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craniofacial
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• exhibit skull shape alterations, including, depression across the bridge of the nose and eye socket, and an outward displacement of the frontal and occipital bones
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• have small, white upper and lower incisors that are prone to breakage, instead of the normal yellow, enamel covered teeth
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• very thin, porous enamel layer that is almost non-existent in some areas
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• lower incisors are prone to breakage
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cardiovascular system
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• pronounced reduction in myocardial gap junctions
• exhibit small, multifocal lesions of myocardial mineralization
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• patent foramen ovale is seen in 2 of 5 mutants
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• mild fibrosis
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• 2 of 9 exhibit abnormal cardiac conduction and/or contraction defects
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• 50-60 week old mutants exhibit elevated pre-ejection and ejection times of the left ventricle, increased diastolic chamber dilation, and reduced relative diastolic wall thickness
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• 50-60 week old mutants exhibit reduced right ventricular fractional shortening and diastolic wall thickness, suggesting development of right ventricular failure with aging
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• premature ventricular contractions (ectopic beats) occurred during 1-min ECG recording in one heterozygote
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• 2 of 9 exhibit abnormal cardiac conduction and/or contraction defects
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• prolonged PR interval and elevated myocardial performance index in one heterozygote
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• prolonged QRS duration occurred during 1-min ECG recording in one heterozygote
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muscle
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• pronounced reduction in myocardial gap junctions
• exhibit small, multifocal lesions of myocardial mineralization
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• 2 of 9 exhibit abnormal cardiac conduction and/or contraction defects
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• 50-60 week old mutants exhibit elevated pre-ejection and ejection times of the left ventricle, increased diastolic chamber dilation, and reduced relative diastolic wall thickness
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• 50-60 week old mutants exhibit reduced right ventricular fractional shortening and diastolic wall thickness, suggesting development of right ventricular failure with aging
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vision/eye
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• 2 of 4 mice that have corneal opacity also have iris malformations
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• seen in 2 of 4 mutants that have corneal opacity
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• seen in 4 of 16 mutants at 5-34 weeks of age
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hematopoietic system
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• bone marrow atrophy and associated hypocellularity in conjunction with increased adipogenesis is seen in young mice (8 weeks) and progresses with age (17-51 weeks)
• frequency of most mature hematopoietic lineages and their progenitors within the bone marrow are increased
• bone marrow side population cells are increased 2.4-fold at 15 weeks of age and 3.5-fold at 57-62 weeks of age
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• bone marrow hypocellularity
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• erythroblasts and their progenitors are decreased in total number and frequency
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immune system
behavior/neurological
| N |
• do not detect weakness of limbs or abnormal gait
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hearing/vestibular/ear
| N |
• do not detect any hearing abnormalities
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reproductive system
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• TUNEL analysis indicated a significant increase of granulosa cell apoptosis in the antral follicles of mutant ovaries
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• mutant granulosa cells exhibit a reduced proliferation rate relative to wild-type cells
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• at P1, mutant ovaries contain normal numbers of germ cells; however, the numerous gap junction 'plaques' present in wild-type ovaries, are rarely found in mutant ovaries
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• mutant granulosa cells display aberrant phosphorylation and trafficking of Cx43 protein: whereas the abundance of total protein is not significantly altered, the phosphorylated P1 and P2 forms are significantly reduced, and very few gap junction plaques are observed
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• ovaries of sexually mature female mutants contain significantly fewer pre-ovulatory follicles at proestrus than wild-type females
• however, no significant differences in the number of early antral follicles are observed
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• significantly fewer oocytes are collected from the oviducts of mutant females (19.6 +/- 9.5) relative to wild-type females (60.0 +/- 3.8) after priming with eCG and hCG
• however, after in vitro fertilization, mutant oocytes are able to develop to the two-cell stage at a frequency similar to that of wild-type oocytes
• in vitro, mutant oocytes are equally as competent as wild-type oocytes in undergoing the first meiotic division to produce the first polar body
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• the pregnancy rate of mutant females mated with wild-type males is significantly lower (23.5%) than that of wild-type females (83.9%)
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• after mating with wild-type males, mutant females show a significant reduction in mean litter size relative to wild-type females (3.0 +/- 0.2 vs 7.9 +/- 0.3 pups/litter, respectively)
• only ~16% of pups born to mutant females survive beyond P1, at least partly due to a existing lactation defect
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endocrine/exocrine glands
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• TUNEL analysis indicated a significant increase of granulosa cell apoptosis in the antral follicles of mutant ovaries
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• mutant granulosa cells exhibit a reduced proliferation rate relative to wild-type cells
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• at P1, mutant ovaries contain normal numbers of germ cells; however, the numerous gap junction 'plaques' present in wild-type ovaries, are rarely found in mutant ovaries
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• mutant granulosa cells display aberrant phosphorylation and trafficking of Cx43 protein: whereas the abundance of total protein is not significantly altered, the phosphorylated P1 and P2 forms are significantly reduced, and very few gap junction plaques are observed
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• ovaries of sexually mature female mutants contain significantly fewer pre-ovulatory follicles at proestrus than wild-type females
• however, no significant differences in the number of early antral follicles are observed
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integument
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| oculodentodigital dysplasia | DOID:0060291 |
OMIM:164200 OMIM:257850 |
J:101733 | |
