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Phenotypes Associated with This Genotype
Genotype
MGI:3777944
Allelic
Composition
Ubbtm1Rrk/Ubbtm1Rrk
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ubbtm1Rrk mutation (1 available); any Ubb mutation (18 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Adult-onset degeneration of hypothalamic neurons in Ubbtm1Rrk/Ubbtm1Rrk mice

cellular
• increase in apoptosis in oocytes due to meiotic arrest
• fetal ovaries have fewer oocytes and elevated apoptotic nuclei
• oocytes from superovulated females have a thin zona pellucida that is tightly adherent to the plasma membrane
• germ cells fail to progress beyond the early pachytene spermatocyte stage of meiosis and undergo cell death, such that by by 8.5 months of age, no germ cells are present

growth/size/body
• mutants exhibit adult-onset obesity
• newborns are smaller, however by 16 weeks of age, body weights are similar to wild-type
• mutants exhibit a subtle linear growth retardation after birth

adipose tissue
• body fat content is elevated in adults and is associated with reduced lean body mass and a corresponding increase in fat mass and not due to an increase in total body mass

behavior/neurological
• the compensatory hyperphagia that is seen in wild-type mice after food deprivation is substantially blunted in adult mutants

homeostasis/metabolism
• serum leptin levels are elevated in adults, even after food deprivation
• however, blood glucose and serum insulin levels are normal in adult obese mutants
• the compensatory hyperphagia that is seen in wild-type mice after food deprivation is substantially blunted in adult mutants and they show impaired body weight recovery after fasting

nervous system
• total neuron counts in the arcuate nucleus of the hypothalamus are reduced by about 30% in 3-month old mutants
• progressive neuron degeneration in the arcuate nucleus of the hypothalamus

reproductive system
• few corpora lutea are seen at 2 and 5 months of age
• ovaries of 2 and 5 month old females contain few mature follicles
• following treatment with PMSG, females form normal antral follicles in which oocytes contain a normal-appearing germinal vesicle, however the size of the antral follicles is smaller
• ovarian size is significantly reduced at 5 months of age
• 5 month old ovaries weigh on average 2-3 times less than control ovaries
• seminiferous tubules are smaller by 19 days of age and by 40 days, the lumen of the seminiferous tubules is absent
• testes fail to increase in size with age, such that at 5 months of age, testes are significantly smaller than in wild-type and by 8.5 months, testes are severely atrophic
• however, Leydig cell function appears normal
• by 8.5 months, testes are severely atrophic
• progressive testes degeneration
• increase in apoptosis in oocytes due to meiotic arrest
• fetal ovaries have fewer oocytes and elevated apoptotic nuclei
• oocytes from superovulated females have a thin zona pellucida that is tightly adherent to the plasma membrane
• germ cells fail to progress beyond the early pachytene spermatocyte stage of meiosis and undergo cell death, such that by by 8.5 months of age, no germ cells are present
• oocytes exhibit a heteromorphic meiotic arrest but do not proceed beyond metaphase I
• nuclear envelope dissolution is delayed and is observed in fewer than 70% of oocytes, indicating that oocytes cannot exit meiotic prophase and that those that exit prophase cannot complete meiosis I
• chromosomes from oocytes only rarely align on a normal-looking spindle, indicating that oocytes cannot get through the prophase-to-metaphase transition
• spermatogenesis is arrested in prophase of meiosis I, before metaphase of the first meiotic division
• females superovulated with follicle-stimulating hormone and luteinizing hormone rarely ovulate any oocytes

endocrine/exocrine glands
• few corpora lutea are seen at 2 and 5 months of age
• ovaries of 2 and 5 month old females contain few mature follicles
• following treatment with PMSG, females form normal antral follicles in which oocytes contain a normal-appearing germinal vesicle, however the size of the antral follicles is smaller
• ovarian size is significantly reduced at 5 months of age
• 5 month old ovaries weigh on average 2-3 times less than control ovaries
• seminiferous tubules are smaller by 19 days of age and by 40 days, the lumen of the seminiferous tubules is absent
• testes fail to increase in size with age, such that at 5 months of age, testes are significantly smaller than in wild-type and by 8.5 months, testes are severely atrophic
• however, Leydig cell function appears normal
• by 8.5 months, testes are severely atrophic
• progressive testes degeneration


Contributing Projects:
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
04/09/2024
MGI 6.23
The Jackson Laboratory