Phenotypes Associated with This Genotype

Genotype
MGI:3613012

• Allelic Composition: Ncoa3^tm1Jxu/Ncoa3^tm1Jxu
• Genetic Background: involves: 129S6/SvEvTac

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

Alveolar formation is reduced in the Ncoa3^tm1Jxu/Ncoa3^tm1Jxu mammary gland.

mortality/aging

preweaning lethality, incomplete penetrance ( J:62724 )

• at weaning, homozygotes are present at a reduced Mendelian frequency (16% vs 25%)

reproductive system

abnormal vagina epithelium morphology ( J:62724 )

♀ • at P29, female homozygotes show a poorly developed thin vaginal epithelial layer, little secretion, and a tightly closed vagina

delayed sexual maturation ( J:62724 )

♀ • female homozygotes display a pubertal delay that is, at least partially, due to a decrease in systemic estrogen levels

delayed vaginal opening ( J:62724 )

♀ • the average ages of vaginal opening time are at P26.1, P26.5, and P34.4 for wild-type, heterozygous, and homozygous females, respectively

♀ • delayed vaginal opening can be rescued with estradiol treatment

abnormal female reproductive system physiology ( J:62724 )

♀ • female homozygotes have compromised reproductive function, with only 36% becoming pregnant after successful mating to wild-type males vs 75% of wild-type and heterozygous females

decreased superovulation rate ( J:62724 )

♀ • upon hormonal treatment, all wild-type females can be induced to superovulate with an average of 23.7 5.5 eggs per mouse; in contrast, only 60% of homozygotes ovulate with 10.4 3.8 eggs produced per mouse

♀ • no mature follicles are observed in the ovaries of female mutants that fail to ovulate

prolonged estrous cycle ( J:62724 )

♀ • female homozygotes exhibit significantly prolonged estrous cycles relative to wild-type females (14.6 2.7 days vs 8.1 2.4 days)

decreased litter size ( J:62724 )

• female homozygotes produce only 4.6 0.5 pups per litter vs 7.3 1.6 pups per litter produced by wild-type mothers

growth/size/body

decreased body weight ( J:62724 )

• adult male homozygotes show a 30% reduction in average body weight relative to wild-type males

• adult female homozygotes show a 15%-20% reduction in average body weight relative to wild-type females

cachexia ( J:62724 )

• ~10% of homozygotes display wasting syndrome, including weight loss, eye and skin infection, decreased mobility, arched back, and death at various ages

disproportionate dwarf ( J:62724 )

postnatal growth retardation ( J:62724 )

• female homozygotes display a relatively normal growth until P9, followed by a significant decrease in growth rate at P9-P21, and severely pronounced retardation after P21

• male homozygotes display a relatively normal growth until P28, followed by a severe progressive growth retardation after P35

endocrine/exocrine glands

abnormal mammary gland development ( J:62724 )

♀ • female homozygotes display delayed mammary gland ductal growth; estrogen therapy successfully rescues the growth deficiency of mammary ducts without changing IGF-1 levels

♀ • female homozygotes show a dramatic decrease in mammary gland alveolar development in response to combined stimulation with 17beta -estradiol and progesterone

abnormal branching of the mammary ductal tree ( J:62724 )

♀ • by 2 months, ductal branches penetrate only about 2/3 of the mutant mammary fat pad; ductal growth does not penetrate the entire fat pad until 11 weeks

homeostasis/metabolism

decreased circulating estradiol level ( J:62724 )

♀ • at P29 (i.e. before vaginal opening), female homozygotes exhibit only 60% of wild-type serum 17beta-estradiol levels

♀ • although serum estradiol levels show a progressive increase at later stages, they remain significantly lower than wild-type levels

decreased circulating insulin-like growth factor I level ( J:62724 )

• growth retardation is associated with a ~40% reduction in serum IGF-1 levels in both sexes; no statistical differences in GH levels are observed

integument

abnormal mammary gland development ( J:62724 )

♀ • female homozygotes display delayed mammary gland ductal growth; estrogen therapy successfully rescues the growth deficiency of mammary ducts without changing IGF-1 levels

♀ • female homozygotes show a dramatic decrease in mammary gland alveolar development in response to combined stimulation with 17beta -estradiol and progesterone

abnormal branching of the mammary ductal tree ( J:62724 )

♀ • by 2 months, ductal branches penetrate only about 2/3 of the mutant mammary fat pad; ductal growth does not penetrate the entire fat pad until 11 weeks

rough coat ( J:62724 )

• homozygotes display a rough and dull hair coat

cellular

decreased fibroblast cell migration ( J:88789 )

• mouse embryonic fibroblasts exhibit decreased migration compared with wild-type cells