Analysis Tools
mortality/aging
|
• seen in 46 of 170 heterozygotes; time not specified
|
cellular
 |
• TUNEL analysis indicated a significant increase of granulosa cell apoptosis in the antral follicles of mutant ovaries
|
|
|
• mutant granulosa cells exhibit a reduced proliferation rate relative to wild-type cells
|
growth/size/body
|
• have small, white upper and lower incisors that are prone to breakage, instead of the normal yellow, enamel covered teeth
|
|
• very thin, porous enamel layer that is almost non-existent in some areas
|
|
• lower incisors are prone to breakage
|
limbs/digits/tail
|
• digit 1 (pollex) on the forelimb consists of a thickened, malformed bone
|
|
• the middle phalange on the last digit of both the forelimb and hindlimb is absent
|
syndactyly
(
J:101733
)
|
• variable fusion of digits 2, 3, and 4 on all limbs; fusion of soft tissue but not bone
|
skeleton
|
• 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
|
|
• have small, white upper and lower incisors that are prone to breakage, instead of the normal yellow, enamel covered teeth
|
|
• very thin, porous enamel layer that is almost non-existent in some areas
|
|
• lower incisors are prone to breakage
|
|
• the middle phalange on the last digit of both the forelimb and hindlimb is absent
|
craniofacial
|
• 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
|
|
• have small, white upper and lower incisors that are prone to breakage, instead of the normal yellow, enamel covered teeth
|
|
• very thin, porous enamel layer that is almost non-existent in some areas
|
|
• lower incisors are prone to breakage
|
cardiovascular system
|
• pronounced reduction in myocardial gap junctions
• exhibit small, multifocal lesions of myocardial mineralization
|
|
• patent foramen ovale is seen in 2 of 5 mutants
|
|
• mild fibrosis
|
|
• 2 of 9 exhibit abnormal cardiac conduction and/or contraction defects
|
|
• 50-60 week old mutants exhibit reduced right ventricular fractional shortening and diastolic wall thickness, suggesting development of right ventricular failure with aging
• 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
|
|
• premature ventricular contractions (ectopic beats) occurred during 1-min ECG recording in one heterozygote
|
|
• 2 of 9 exhibit abnormal cardiac conduction and/or contraction defects
|
|
• prolonged PR interval and elevated myocardial performance index in one heterozygote
|
|
• prolonged QRS duration occurred during 1-min ECG recording in one heterozygote
|
muscle
|
• pronounced reduction in myocardial gap junctions
• exhibit small, multifocal lesions of myocardial mineralization
|
|
• 2 of 9 exhibit abnormal cardiac conduction and/or contraction defects
|
|
• 50-60 week old mutants exhibit reduced right ventricular fractional shortening and diastolic wall thickness, suggesting development of right ventricular failure with aging
• 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
|
vision/eye
|
• 2 of 4 mice that have corneal opacity also have iris malformations
|
|
• seen in 2 of 4 mutants that have corneal opacity
|
|
• seen in 4 of 16 mutants at 5-34 weeks of age
|
hematopoietic system
|
• 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
|
|
• bone marrow hypocellularity
|
|
• erythroblasts and their progenitors are decreased in total number and frequency
|
immune system
behavior/neurological
| N |
• do not detect weakness of limbs or abnormal gait
|
hearing/vestibular/ear
| N |
• do not detect any hearing abnormalities
|
reproductive system
|
|
• TUNEL analysis indicated a significant increase of granulosa cell apoptosis in the antral follicles of mutant ovaries
|
|
|
• mutant granulosa cells exhibit a reduced proliferation rate relative to wild-type cells
|
|
|
• 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
|
|
|
• 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
|
|
|
• 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
|
|
|
• 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
|
|
|
• the pregnancy rate of mutant females mated with wild-type males is significantly lower (23.5%) than that of wild-type females (83.9%)
|
|
• 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
|
endocrine/exocrine glands
|
|
• TUNEL analysis indicated a significant increase of granulosa cell apoptosis in the antral follicles of mutant ovaries
|
|
|
• mutant granulosa cells exhibit a reduced proliferation rate relative to wild-type cells
|
|
|
• 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
|
|
|
• 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
|
|
|
• 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
|
integument
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| oculodentodigital dysplasia | DOID:0060291 |
OMIM:164200 OMIM:257850 |
J:101733 | |
