Phenotypes Associated with This Genotype

Genotype
MGI:2450563

• Allelic Composition: Ace^tm1Unc/Ace^tm1Unc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

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

cellular

impaired sperm migration in female genital tract ( J:46177 )

♂ • very few mutant sperm progress beyond the two oviduct regions nearest the uterus at 1 hr after mating, whereas significantly more wild-type sperm reach the extramural uterotubal junction and the lower and upper isthmus regions of the oviducts under identical conditions

mortality/aging

preweaning lethality, incomplete penetrance ( J:25284 )

• intercrossing of heterozygotes results in about 11% homozygous mutant mice compared with the expected 25%; the cause of this deviation has not been determined

• at weaning, the proportions of wild-type, heterozygous and homozygous offspring differ significantly from the expected 1:2:1 Mendelian ratios

reproductive system

reproductive system phenotype ( J:25284 , J:25284 , J:46177 )

♀N • females are fertile (J:25284)

♂N • males show normal testes morphology, normal spermatogenesis, and normal sperm count and morphology (J:25284)

♂N • sperm show no significant differences in assays of viability, motility, capacitation, and induction of the acrosome reaction relative to wild-type sperm (J:46177)

impaired sperm migration in female genital tract ( J:46177 )

♂ • very few mutant sperm progress beyond the two oviduct regions nearest the uterus at 1 hr after mating, whereas significantly more wild-type sperm reach the extramural uterotubal junction and the lower and upper isthmus regions of the oviducts under identical conditions

decreased litter size ( J:25284 )

• 2 pups in a single litter

reduced male fertility ( J:25284 )

♂ • 80% (4 of 5) males are unable to sire offspring

♂ • reduced fertility putatively due to an impaired ability to fertilize ova

impaired fertilization ( J:46177 )

• mutant sperm show defects in transport within the oviducts and in binding to zonae pellucidae

• even those mutant sperm that reach the oviductal ampulla are less likely to fertilize eggs because of their reduced capacity for zona binding

decreased fertilization frequency ( J:46177 )

• sperm from male homozygotes achieve in vivo fertilization at a reduced frequency: >65% of eggs from wild-type matings become fertilized and develop to the 8-cell stage or beyond compared with <5% of eggs harvested from wild-type females inseminated by homozygous mutant males

impaired binding of sperm to zona pellucida ( J:46177 )

♂ • mutant sperm show defects in binding to zonae pellucidae

cardiovascular system

abnormal kidney vasculature morphology ( J:25284 )

• intrarenal arteries display significant mural hypercellularity and thickening with narrowing of the lumen

hypotension ( J:25284 )

• blood pressure is reduced by ~35 mm Hg in both males and females

renal/urinary system

abnormal kidney vasculature morphology ( J:25284 )

• intrarenal arteries display significant mural hypercellularity and thickening with narrowing of the lumen

kidney inflammation ( J:25284 )

• chronic inflammation

abnormal renal glomerulus morphology ( J:25284 )

• crowding of glomeruli

kidney cortex atrophy ( J:25284 )

• focal areas of cortical thinning

renal tubule atrophy ( J:25284 )

• shrinkage of tubules associated with a wedge-shaped zone of cortical atrophy in the subcapsular renal cortex

immune system

kidney inflammation ( J:25284 )

• chronic inflammation