Phenotypes associated with this allele

• Allele Symbol: Ubb^tm1Rrk
• Allele Name: targeted mutation 1, Ron R Kopito
• Allele ID: MGI:3774112
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ubb^tm1Rrk/Ubb^tm1Rrk	involves: 129S1/Sv * 129X1/SvJ	MGI:5897220
hm2	Ubb^tm1Rrk/Ubb^tm1Rrk	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3777944

Genotype
MGI:5897220

hm1

• Allelic Composition: Ubb^tm1Rrk/Ubb^tm1Rrk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

vision/eye

decreased retina rod cell number ( J:279808 )

• progressive with age; fewer rhodopsin-expressing cells are seen by 3-4 months of age

retina rod cell degeneration ( J:279808 )

thin retina outer nuclear layer ( J:279808 )

• progressive with age; reduced ONL thickness was evident in 1 month old adult homozygous mutant mice and a greater reduction in ONL thickness was seen in older 3-4 month old adult mutant mice

retina degeneration ( J:279808 )

nervous system

decreased retina rod cell number ( J:279808 )

• progressive with age; fewer rhodopsin-expressing cells are seen by 3-4 months of age

retina rod cell degeneration ( J:279808 )

Genotype
MGI:3777944

hm2

• Allelic Composition: Ubb^tm1Rrk/Ubb^tm1Rrk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Adult-onset degeneration of hypothalamic neurons in Ubb^tm1Rrk/Ubb^tm1Rrk mice

cellular

abnormal oocyte morphology ( J:130361 )

♀ • increase in apoptosis in oocytes due to meiotic arrest

decreased oocyte number ( J:130361 )

♀ • fetal ovaries have fewer oocytes and elevated apoptotic nuclei

thin zona pellucida ( J:130361 )

♀ • oocytes from superovulated females have a thin zona pellucida that is tightly adherent to the plasma membrane

decreased male germ cell number ( J:130361 )

♂ • 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

increased susceptibility to age related obesity ( J:132767 )

• mutants exhibit adult-onset obesity

decreased body size ( J:132767 )

• newborns are smaller, however by 16 weeks of age, body weights are similar to wild-type

decreased body length ( J:132767 )

postnatal growth retardation ( J:132767 )

• mutants exhibit a subtle linear growth retardation after birth

adipose tissue

increased total body fat amount ( J:132767 )

• 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

decreased compensatory feeding amount ( J:132767 )

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

homeostasis/metabolism

increased circulating leptin level ( J:132767 )

• serum leptin levels are elevated in adults, even after food deprivation

• however, blood glucose and serum insulin levels are normal in adult obese mutants

abnormal energy homeostasis ( J:132767 )

• 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

abnormal hypothalamus morphology ( J:132767 )

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

neuron degeneration ( J:132767 )

• progressive neuron degeneration in the arcuate nucleus of the hypothalamus

reproductive system

decreased corpora lutea number ( J:130361 )

♀ • few corpora lutea are seen at 2 and 5 months of age

decreased mature ovarian follicle number ( J:130361 )

♀ • ovaries of 2 and 5 month old females contain few mature follicles

abnormal tertiary ovarian follicle morphology ( J:130361 )

♀ • 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

small ovary ( J:130361 )

♀ • ovarian size is significantly reduced at 5 months of age

decreased ovary weight ( J:130361 )

♀ • 5 month old ovaries weigh on average 2-3 times less than control ovaries

small seminiferous tubules ( J:130361 )

♂ • seminiferous tubules are smaller by 19 days of age and by 40 days, the lumen of the seminiferous tubules is absent

small testis ( J:130361 )

♂ • 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

testicular atrophy ( J:130361 )

♂ • by 8.5 months, testes are severely atrophic

testis degeneration ( J:130361 )

♂ • progressive testes degeneration

abnormal gametogenesis ( J:130361 )

abnormal oocyte morphology ( J:130361 )

♀ • increase in apoptosis in oocytes due to meiotic arrest

decreased oocyte number ( J:130361 )

♀ • fetal ovaries have fewer oocytes and elevated apoptotic nuclei

thin zona pellucida ( J:130361 )

♀ • oocytes from superovulated females have a thin zona pellucida that is tightly adherent to the plasma membrane

decreased male germ cell number ( J:130361 )

♂ • 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

abnormal female meiosis ( J:130361 )

♀ • 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

arrest of male meiosis ( J:130361 )

♂ • spermatogenesis is arrested in prophase of meiosis I, before metaphase of the first meiotic division

failure of superovulation ( J:130361 )

♀ • females superovulated with follicle-stimulating hormone and luteinizing hormone rarely ovulate any oocytes

female infertility ( J:130361 )

♀

male infertility ( J:130361 )

♂

endocrine/exocrine glands

decreased corpora lutea number ( J:130361 )

♀ • few corpora lutea are seen at 2 and 5 months of age

decreased mature ovarian follicle number ( J:130361 )

♀ • ovaries of 2 and 5 month old females contain few mature follicles

abnormal tertiary ovarian follicle morphology ( J:130361 )

♀ • 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

small ovary ( J:130361 )

♀ • ovarian size is significantly reduced at 5 months of age

decreased ovary weight ( J:130361 )

♀ • 5 month old ovaries weigh on average 2-3 times less than control ovaries

small seminiferous tubules ( J:130361 )

♂ • seminiferous tubules are smaller by 19 days of age and by 40 days, the lumen of the seminiferous tubules is absent

small testis ( J:130361 )

♂ • 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

testicular atrophy ( J:130361 )

♂ • by 8.5 months, testes are severely atrophic

testis degeneration ( J:130361 )

♂ • progressive testes degeneration