Phenotypes associated with this allele

• Allele Symbol: Ncoa6^tm1Jkr
• Allele Name: targeted mutation 1, Janardan K Reddy
• Allele ID: MGI:2448995
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ncoa6^tm1Jkr/Ncoa6^tm1Jkr Tg(MMTV-cre)FMam/?	involves: 129P2/OlaHsd * FVB	MGI:3810657
cn2	Ncoa6^tm1Jkr/Ncoa6^tm1Jkr Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * FVB/N	MGI:6276351
cn3	Ncoa6^tm1Jkr/Ncoa6^+ Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * FVB/N	MGI:6276352

Genotype
MGI:3810657

cn1

• Allelic Composition: Ncoa6^tm1Jkr/Ncoa6^tm1Jkr; Tg(MMTV-cre)FMam/?
• Genetic Background: involves: 129P2/OlaHsd * FVB

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

Retarded ductal branching of Ncoa6^tm1Jkr/Ncoa6^tm1Jkr Tg(MMTV-cre)FMam/? mammary glands during puberty

endocrine/exocrine glands

abnormal mammary gland development ( J:121207 )

♀ • defective mammopoiesis during puberty, pregnancy, and lactation

abnormal branching of the mammary ductal tree ( J:121207 )

♀ • mammary glands show a normal elongation of ducts but a decreased number of ductal branches and reduced density of ducts during puberty and long after puberty

♀ • ductal branching stimulated by direct estrogen treatment of ovariectomized females is attenuated in mutants

abnormal mammary gland growth during lactation ( J:121207 )

♀ • lactating mammary glands contain decreased numbers of lobuloalveoli with many adipoctyes

abnormal mammary gland growth during pregnancy ( J:121207 )

♀ • glands from females on the 15th day of pregnancy show impaired lobuloalveolar development with decreased density of alveoli

abnormal mammary duct terminal end bud morphology ( J:121207 )

♀ • slight increase in apoptosis is seen in the terminal end buds of mutant inguinal mammary glands

hypolactation ( J:121207 )

♀ • most pups from mutant litters die within 48 hours after birth with no milk in stomachs, however pups can be fostered by wild-type females, indicating inability to produce a sufficient amount of milk to nurse pups

reproductive system

abnormal mammary gland growth during pregnancy ( J:121207 )

♀ • glands from females on the 15th day of pregnancy show impaired lobuloalveolar development with decreased density of alveoli

integument

abnormal mammary gland development ( J:121207 )

♀ • defective mammopoiesis during puberty, pregnancy, and lactation

abnormal branching of the mammary ductal tree ( J:121207 )

♀ • mammary glands show a normal elongation of ducts but a decreased number of ductal branches and reduced density of ducts during puberty and long after puberty

♀ • ductal branching stimulated by direct estrogen treatment of ovariectomized females is attenuated in mutants

abnormal mammary gland growth during lactation ( J:121207 )

♀ • lactating mammary glands contain decreased numbers of lobuloalveoli with many adipoctyes

abnormal mammary gland growth during pregnancy ( J:121207 )

♀ • glands from females on the 15th day of pregnancy show impaired lobuloalveolar development with decreased density of alveoli

abnormal mammary duct terminal end bud morphology ( J:121207 )

♀ • slight increase in apoptosis is seen in the terminal end buds of mutant inguinal mammary glands

hypolactation ( J:121207 )

♀ • most pups from mutant litters die within 48 hours after birth with no milk in stomachs, however pups can be fostered by wild-type females, indicating inability to produce a sufficient amount of milk to nurse pups

Genotype
MGI:6276351

cn2

• Allelic Composition: Ncoa6^tm1Jkr/Ncoa6^tm1Jkr; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:269856 )

• mice start to die after 2 months of age, with an approximate 40% survival at 8 months of age

cardiovascular system

abnormal heart morphology ( J:269856 )

• cardiac lipid accumulation

• hearts show disarray of mitochondria, a decrease in the number of mitochondria, and impaired activity of mitochondrial complex II

increased heart weight ( J:269856 )

• increase heart weight-to-body weight ratios

• increase in heart weight is caused by atrial thrombi

• however, ventricle weight is not altered

cardiac hypertrophy ( J:269856 )

• hearts show increased expression of cardiac hypertrophy markers at 12 and 20 months of age but not a 4 weeks of age

• hearts of 12 week old mice show a hypertrophic phenotype, indicating that concentric hypertrophy transiently proceeds prior to dilated cardiomyopathy

dilated heart ( J:269856 )

• cardiac dilatation

dilated heart left ventricle ( J:269856 )

dilated cardiomyopathy ( J:269856 )

• hearts show features of dilated cardiomyopathy, including enlarged ventricular cavities with thin walls and reactive myocardial fibrosis

decreased cardiac muscle contractility ( J:269856 )

• diminished ejection fraction and fractional shortening

abnormal heart echocardiography feature ( J:269856 )

• echocardiography indicates severe dilatation of the left ventricle, decreased contractility without alteration in heart rate, diminished ejection fraction and fractional shortening, and enlarged left ventricular end-systolic dimensions and end-diastolic dimensions at 4 months of age

cellular

decreased mitochondrial number ( J:269856 )

• hearts show a decrease in the number of mitochondria

homeostasis/metabolism

abnormal atrial thrombosis ( J:269856 )

• atrial thrombi

abnormal lipid level ( J:269856 )

• cardiac lipid accumulation

muscle

dilated cardiomyopathy ( J:269856 )

• hearts show features of dilated cardiomyopathy, including enlarged ventricular cavities with thin walls and reactive myocardial fibrosis

decreased cardiac muscle contractility ( J:269856 )

• diminished ejection fraction and fractional shortening

abnormal sarcomere morphology ( J:269856 )

• disarray of sarcomeres in hearts

growth/size/body

increased heart weight ( J:269856 )

• increase heart weight-to-body weight ratios

• increase in heart weight is caused by atrial thrombi

• however, ventricle weight is not altered

cardiac hypertrophy ( J:269856 )

• hearts show increased expression of cardiac hypertrophy markers at 12 and 20 months of age but not a 4 weeks of age

• hearts of 12 week old mice show a hypertrophic phenotype, indicating that concentric hypertrophy transiently proceeds prior to dilated cardiomyopathy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:269856

Genotype
MGI:6276352

cn3

• Allelic Composition: Ncoa6^tm1Jkr/Ncoa6⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

cardiovascular system

dilated cardiomyopathy ( J:269856 )

• mice exhibit characteristics of dilated cardiomyopathy with late onset

decreased cardiac muscle contractility ( J:269856 )

• decrease in percent fractional shortening

abnormal heart echocardiography feature ( J:269856 )

• echocardiography indicates decreased fractional shortening and enlarged left ventricular end-systolic dimensions and end-diastolic dimensions

muscle

dilated cardiomyopathy ( J:269856 )

• mice exhibit characteristics of dilated cardiomyopathy with late onset

decreased cardiac muscle contractility ( J:269856 )

• decrease in percent fractional shortening

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:269856