mortality/aging
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• birth rate of double mutant mice is only one third of the expected rate; following mating of double heterozygotes, only 2.1% are recovered at 1 week after birth versus expected 6.25%
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growth/size/body
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• at 3-4 weeks of age, body weight is about half of that in wild-type controls
• adult mice weigh 75-80% of age-matched wild-type controls
• however, no significant differences in body weight are observed 1 week after birth
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• both sexes grow much more slowly than wild-type controls from 2 to 4 weeks after birth and the difference in weight gain is maintained to adulthood
• high-calorie diet feeding fails to result in a greater weight gain than ordinary feeding, unlike in wild-type controls
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behavior/neurological
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• at 1 month of age, spontaneous locomotive activity is 50-60% of that in wild-type controls; both male and female mice are affected
(J:123392)
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• at 3 months of age, spontaneous locomotive activity is still ~80% of that in wild-type males
(J:123392)
• however, spontaneous locomotive activity is normal in females at 3 months
(J:123392)
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digestive/alimentary system
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• all organs of the digestive tract are smaller than those in wild-type controls
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• mice exhibit poor growth of the mucosal epithelium in the descending colon, but not in other organs of the digestive tract
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• colon shows poor growth, esp. in the mucosal layer of the descending colon
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reproductive system
N |
• male mice are fertile with normal reproductive capabilities relative to wild-type controls
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• at 4 weeks of age, the number of mature follicles with a single, fused antrum is lower than that in wild-type controls
• however, the total number of follicles (double layered primary follicles and follicles at more advanced stages of maturation) is normal
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• females exhibit poor maturation of ovarian follicles
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• at 4 weeks of age, ovary size is about 60% of that in wild-type controls
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• at 10 months of age, the vaginal epithelium is thinner and shows inward projections, indicating vaginal epithelium atrophy
• at 2 months of age, vaginal epithelium thickness is normal, but the multilayered structure of the epithelium is disordered, the nuclear size of the epithelial cells is uneven and condensed chromatins are frequently observed
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• at 10 months of age, 8 of 19 (42%) of mice exhibit vaginal malformations at the opening, unlike single homozygotes
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• many mice show narrow vaginas that are frequently divided into two parts
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• in females with vaginal malformations, the vaginal lumen is frequently divided into two parts by a wall
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• at 10 months of age, the vaginal epithelium is thinner and shows inward projections, indicating vaginal epithelium atrophy
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• following administration of PMS-hCG to 8-10-week-old mice, the number of ovulated ova is significantly lower than that in similarly treated wild-type controls
• however, the % of ova that reach the 2-cell stage after in vitro fertilization is normal
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• diestrus period is longer than in wild-type controls; diestrus to proestrus occupies about 4 days in the 6-day estrous cycle
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• estrus period lasts only for 1 day in the 6-day estrous cycle versus 2-3 days in wild-type controls
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• proestrus period is longer than in wild-type controls; diestrus to proestrus occupies about 4 days in the 6-day estrous cycle
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• 19 of 24 female mice (79%) are sterile
• all females with an abnormal vagina are sterile, without any sign of a plug; on the other hand, 7 of 11 females with a normal vagina are sterile
• superovulation fails to significantly increase the fertility of female mice
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endocrine/exocrine glands
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• at 4 weeks of age, the number of mature follicles with a single, fused antrum is lower than that in wild-type controls
• however, the total number of follicles (double layered primary follicles and follicles at more advanced stages of maturation) is normal
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• females exhibit poor maturation of ovarian follicles
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• at 4 weeks of age, ovary size is about 60% of that in wild-type controls
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hearing/vestibular/ear
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• mice exhibit severe auditory deficits
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