Phenotypes associated with this allele

• Allele Symbol: Ncoa3^tm1Jxu
• Allele Name: targeted mutation 1, Jianming Xu
• Allele ID: MGI:1931860
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ncoa3^tm1Jxu/Ncoa3^tm1Jxu	involves: 129S6/SvEvTac	MGI:3613012
hm2	Ncoa3^tm1Jxu/Ncoa3^tm1Jxu	involves: 129S6/SvEvTac * C57BL/6	MGI:5002620
hm3	Ncoa3^tm1Jxu/Ncoa3^tm1Jxu	involves: 129S6/SvEvTac * C57BL/6J	MGI:5002535
cx4	Ncoa3^tm1Jxu/Ncoa3^+ Tg(MMTV-vHaras)SH1Led/0	involves: 129S6/SvEvTac * C57BL/6J * CD-1	MGI:5002487
cx5	Ncoa3^tm1Jxu/Ncoa3^tm1Jxu Tg(MMTV-vHaras)SH1Led/0	involves: 129S6/SvEvTac * C57BL/6J * CD-1	MGI:5002489

Genotype
MGI:3613012

hm1

• 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

Genotype
MGI:5002620

hm2

• Allelic Composition: Ncoa3^tm1Jxu/Ncoa3^tm1Jxu
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:120086 )

• 1 of 13 LPS-treated mice survives unlike all similarly treated wild-type mice

• however, dexamethasone treatment rescues LPS-induced lethality

immune system

increased circulating interleukin-1 beta level ( J:120086 )

• in LPS-treated mice

increased circulating interleukin-6 level ( J:120086 )

• in LPS-treated mice

increased circulating tumor necrosis factor level ( J:120086 )

• in LPS-treated mice

• however, dexamethasone treatment rescues TNF serum levels

decreased interleukin-1 beta secretion ( J:120086 )

• in LPS-stimulated macrophage

increased interleukin-6 secretion ( J:120086 )

• in LPS-stimulated macrophage

increased tumor necrosis factor secretion ( J:120086 )

• in LPS-stimulated macrophage

• however, dexamethasone-induced TNF production is normal

increased susceptibility to endotoxin shock ( J:120086 )

• LPS-treated mice exhibit increased symptoms of endotoxic shock (crouched position, shivering, ruffled fur, decreased blood glucose, and decreased body temperature), increased serum cytokines (TNF, IL6, and IL1b), increased cytokine production (TNF, IL6, and IL1b), and decreased survival compared with similarly treated wild-type mice

• however, LPS-induced liver damage is normal and dexamethasone treatment rescues LPS-induced TNF production, decreased body temperature, and lethality

increased susceptibility to bacterial infection induced morbidity/mortality ( J:120086 )

• 1 of 13 LPS-treated mice survives unlike all similarly treated wild-type mice

• however, dexamethasone treatment rescues LPS-induced lethality

homeostasis/metabolism

impaired adaptive thermogenesis ( J:120086 )

• in LPS-treated mice

• however, dexamethasone treatment rescues LPS-induced body temperature decrease

decreased circulating glucose level ( J:120086 )

• in LPS-treated mice

increased circulating interleukin-1 beta level ( J:120086 )

• in LPS-treated mice

increased circulating interleukin-6 level ( J:120086 )

• in LPS-treated mice

increased circulating tumor necrosis factor level ( J:120086 )

• in LPS-treated mice

• however, dexamethasone treatment rescues TNF serum levels

Genotype
MGI:5002535

hm3

• Allelic Composition: Ncoa3^tm1Jxu/Ncoa3^tm1Jxu
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

mortality/aging

premature death ( J:109522 )

• survival is decreased 7-fold at 14 months of age

immune system

decreased splenocyte apoptosis ( J:109522 )

increased B cell proliferation ( J:109522 )

• when stimulated with anti-IgM and anti-CD40 antibodies

increased T cell proliferation ( J:109522 )

• when stimulated with anti-CD3 antibodies with or without anti-CD28 antibodies

enlarged spleen ( J:109522 )

• 1.6-fold at 3 months

• 2.14-fold at 14 months

abnormal lymphopoiesis ( J:109522 )

• despite normal T and B cell precursor populations in the thymus, mice exhibit an expansion of lymphoid population due to increased proliferation compared to in wild-type mice

increased leukocyte cell number ( J:109522 )

• increasing with age

increased lymphocyte cell number ( J:109522 )

• increasing with age

increased B cell number ( J:109522 )

• in bone marrow, spleen, lymph nodes, and thymus

increased CD4-positive, alpha-beta T cell number ( J:109522 )

• in bone marrow, spleen, lymph nodes, and thymus

increased CD8-positive, alpha-beta T cell number ( J:109522 )

• in bone marrow, spleen, lymph nodes, and thymus

abnormal B cell morphology ( J:109522 )

• B cells invade marginal sinuses and are increased in number in the red pulp compared to in wild-type mice

abnormal spleen red pulp morphology ( J:109522 )

• B cells invade marginal sinuses and are increased in number in the red pulp compared to in wild-type mice

increased spleen germinal center size ( J:109522 )

• hyperplastic in the lymph nodes and spleen with normal cellularity

adipose tissue

abnormal adipose tissue morphology ( J:117159 )

• mouse embryonic fibroblast exhibit severely impaired adipogenesis compared with wild-type cells

decreased brown adipose tissue amount ( J:144060 )

• mice fed a high-fat diet exhibit decreased intrascapular brown adipose tissue compared with similarly treated wild-type mice

decreased white adipose tissue amount ( J:117159 , J:144060 )

• mice fed a high-fat diet exhibit decreased epididymal white adipose tissue compared with similarly treated wild-type mice (J:144060)

decreased total body fat amount ( J:117159 , J:144060 )

• in mice fed standard chow or a high-fat diet (J:144060)

abnormal brown fat cell morphology ( J:144060 )

• mice fed standard chow exhibit increased mitochondria in the brown adipose tissue compared with wild-type mice

decreased brown fat cell lipid droplet size ( J:144060 )

• in mice fed a high-fat diet

decreased brown fat cell size ( J:144060 )

• in mice fed a high-fat diet

decreased white fat cell size ( J:117159 )

abnormal epididymal fat pad morphology ( J:117159 )

• the epididymal fat pad is smaller than in wild-type mice

decreased epididymal fat pad weight ( J:117159 )

neoplasm

increased lymphoma incidence ( J:109522 )

• in old mice

increased B cell derived lymphoma incidence ( J:109522 )

• in old mice

growth/size/body

decreased body weight ( J:109522 , J:117159 , J:144060 )

• when fed standard chow or a high-fat diet (J:144060)

decreased susceptibility to diet-induced obesity ( J:144060 )

• in mice fed a high-fat diet

enlarged spleen ( J:109522 )

• 1.6-fold at 3 months

• 2.14-fold at 14 months

cellular

increased mitochondrial size ( J:144060 )

• mitochondrial in brown adipose tissue and muscles of mice fed standard chow are larger than wild-type mitochondria

decreased splenocyte apoptosis ( J:109522 )

abnormal cell differentiation ( J:117159 )

• mouse embryonic fibroblast exhibit severely impaired adipogenesis compared with wild-type cells

increased B cell proliferation ( J:109522 )

• when stimulated with anti-IgM and anti-CD40 antibodies

increased T cell proliferation ( J:109522 )

• when stimulated with anti-CD3 antibodies with or without anti-CD28 antibodies

hematopoietic system

decreased splenocyte apoptosis ( J:109522 )

increased B cell proliferation ( J:109522 )

• when stimulated with anti-IgM and anti-CD40 antibodies

increased T cell proliferation ( J:109522 )

• when stimulated with anti-CD3 antibodies with or without anti-CD28 antibodies

enlarged spleen ( J:109522 )

• 1.6-fold at 3 months

• 2.14-fold at 14 months

abnormal lymphopoiesis ( J:109522 )

• despite normal T and B cell precursor populations in the thymus, mice exhibit an expansion of lymphoid population due to increased proliferation compared to in wild-type mice

thrombocytopenia ( J:109522 )

increased leukocyte cell number ( J:109522 )

• increasing with age

increased lymphocyte cell number ( J:109522 )

• increasing with age

increased B cell number ( J:109522 )

• in bone marrow, spleen, lymph nodes, and thymus

increased CD4-positive, alpha-beta T cell number ( J:109522 )

• in bone marrow, spleen, lymph nodes, and thymus

increased CD8-positive, alpha-beta T cell number ( J:109522 )

• in bone marrow, spleen, lymph nodes, and thymus

abnormal B cell morphology ( J:109522 )

• B cells invade marginal sinuses and are increased in number in the red pulp compared to in wild-type mice

abnormal spleen red pulp morphology ( J:109522 )

• B cells invade marginal sinuses and are increased in number in the red pulp compared to in wild-type mice

increased spleen germinal center size ( J:109522 )

• hyperplastic in the lymph nodes and spleen with normal cellularity

homeostasis/metabolism

impaired exercise endurance ( J:144060 )

• mice fed standard chow exhibit increased distance run to exhaustion on a treadmill compared with wild-type mice

decreased circulating glucose level ( J:144060 )

• in mice fed a high-fat diet

decreased circulating insulin level ( J:144060 )

• in mice fed a high-fat diet

decreased circulating cholesterol level ( J:144060 )

• in mice fed a high-fat diet

decreased circulating HDL cholesterol level ( J:144060 )

• in mice fed a high-fat diet

decreased circulating free fatty acids level ( J:144060 )

• in mice fed a high-fat diet

decreased circulating triglyceride level ( J:144060 )

• in mice fed a high-fat diet

increased energy expenditure ( J:144060 )

• in mice fed standard chow

• mice fed a high fat diet exhibit enhanced adaptive thermogenesis compared with wild-type mice

decreased susceptibility to diet-induced obesity ( J:144060 )

• in mice fed a high-fat diet

increased carbon dioxide production ( J:144060 )

• in mice fed standard chow

increased oxygen consumption ( J:144060 )

• in mice fed standard chow

• in isolated muscle fibers

increased respiratory quotient ( J:144060 )

• in mice fed standard chow

improved glucose tolerance ( J:144060 )

• in mice fed standard chow and a high-fat diet

increased insulin sensitivity ( J:144060 )

• in mice fed standard chow or a high-fat diet

liver/biliary system

small liver ( J:144060 )

• in mice fed a high-fat diet

decreased liver weight ( J:144060 )

• in mice fed a high-fat diet

decreased susceptibility to diet-induced hepatic steatosis ( J:144060 )

• livers from mice fed a high-fat diet are less pale than in similarly treated wild-type mice

muscle

abnormal skeletal muscle fiber morphology ( J:144060 )

• muscles from mice fed a standard chow exhibit increased mitochondria size and numbers compared to in wild-type mice

behavior/neurological

impaired exercise endurance ( J:144060 )

• mice fed standard chow exhibit increased distance run to exhaustion on a treadmill compared with wild-type mice

Genotype
MGI:5002487

cx4

• Allelic Composition: Ncoa3^tm1Jxu/Ncoa3⁺; Tg(MMTV-vHaras)SH1Led/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * CD-1

neoplasm

increased mammary gland tumor incidence ( J:88789 )

• by 17 weeks of age, mice exhibit multifocal nodules in the mammary gland and mammary intraepithelial neoplasia lesions

increased mammary adenocarcinoma incidence ( J:88789 )

• by 40 weeks of age

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:88789 )

• by 17 weeks of age, mice exhibit multifocal nodules in the mammary gland and mammary intraepithelial neoplasia lesions

increased mammary adenocarcinoma incidence ( J:88789 )

• by 40 weeks of age

integument

increased mammary gland tumor incidence ( J:88789 )

• by 17 weeks of age, mice exhibit multifocal nodules in the mammary gland and mammary intraepithelial neoplasia lesions

increased mammary adenocarcinoma incidence ( J:88789 )

• by 40 weeks of age

Genotype
MGI:5002489

cx5

• Allelic Composition: Ncoa3^tm1Jxu/Ncoa3^tm1Jxu; Tg(MMTV-vHaras)SH1Led/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * CD-1

neoplasm

decreased mammary gland tumor incidence ( J:88789 )

• only a small proportion of mice older than 35 weeks exhibit mammary intraepithelial neoplasia lesions and mammary tumors compared with Tg(MMTV-vHaras)SH1Led mice

• development of palpable breast tumors is delayed 26 weeks compared with Tg(MMTV-vHaras)SH1Led mice

• by 80 weeks, 25% of mice develop breast tumors compared with all Tg(MMTV-vHaras)SH1Led mice

• ovariectomized mice exhibit complete suppression of breast tumor development

decreased metastatic potential ( J:88789 )

• breast tumors exhibit decreased metastases compared with tumors from Tg(MMTV-vHaras)SH1Led mice

decreased tumor growth/size ( J:88789 )

• breast tumors are smaller in size and exhibit slower growth than tumors from Tg(MMTV-vHaras)SH1Led mice

decreased incidence of induced tumors ( J:88789 )

• mice exhibit delayed hormone-stimulated (via pituitary transplantation) mammary tumorigenesis compared with Tg(MMTV-vHaras)SH1Led mice

cellular

abnormal cell migration ( J:88789 )

• breast tumor cells exhibit decreased migration compared with wild-type cells

decreased mammary gland epithelial cell proliferation ( J:88789 )

♀ • mammary terminal end buds exhibit decreased proliferation compared to in Tg(MMTV-vHaras)SH1Led mice

♀ • cell proliferation in hyperplasia, mammary intraepithelial neoplasia, and tumor lesions is less than in Tg(MMTV-vHaras)SH1Led mice

endocrine/exocrine glands

decreased mammary gland epithelial cell proliferation ( J:88789 )

♀ • mammary terminal end buds exhibit decreased proliferation compared to in Tg(MMTV-vHaras)SH1Led mice

♀ • cell proliferation in hyperplasia, mammary intraepithelial neoplasia, and tumor lesions is less than in Tg(MMTV-vHaras)SH1Led mice

decreased mammary gland tumor incidence ( J:88789 )

• only a small proportion of mice older than 35 weeks exhibit mammary intraepithelial neoplasia lesions and mammary tumors compared with Tg(MMTV-vHaras)SH1Led mice

• development of palpable breast tumors is delayed 26 weeks compared with Tg(MMTV-vHaras)SH1Led mice

• by 80 weeks, 25% of mice develop breast tumors compared with all Tg(MMTV-vHaras)SH1Led mice

• ovariectomized mice exhibit complete suppression of breast tumor development

integument

integument phenotype ( J:88789 )

N • by 80 weeks of age, 50% of mice exhibit normal mammary gland morphology

decreased mammary gland epithelial cell proliferation ( J:88789 )

♀ • mammary terminal end buds exhibit decreased proliferation compared to in Tg(MMTV-vHaras)SH1Led mice

♀ • cell proliferation in hyperplasia, mammary intraepithelial neoplasia, and tumor lesions is less than in Tg(MMTV-vHaras)SH1Led mice

decreased mammary gland tumor incidence ( J:88789 )

• only a small proportion of mice older than 35 weeks exhibit mammary intraepithelial neoplasia lesions and mammary tumors compared with Tg(MMTV-vHaras)SH1Led mice

• development of palpable breast tumors is delayed 26 weeks compared with Tg(MMTV-vHaras)SH1Led mice

• by 80 weeks, 25% of mice develop breast tumors compared with all Tg(MMTV-vHaras)SH1Led mice

• ovariectomized mice exhibit complete suppression of breast tumor development