Phenotypes associated with this allele

• Allele Symbol: Esrrb^tm1.1Nat
• Allele Name: targeted mutation 1.1, Jeremy Nathans
• Allele ID: MGI:3720481
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Esrrb^tm1.1Nat/Esrrb^tm1.1Nat Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6N * FVB/N	MGI:5905569
cn2	Esrrb^tm1.1Nat/Esrrb^tm1.2Nat Edil3^Tg(Sox2-cre)1Amc/Edil3^+	involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL	MGI:3723508
cn3	Esrrb^tm1.1Nat/Esrrb^tm1.2Nat Tg(Nes-cre)1Kln/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:3723507

Genotype
MGI:5905569

cn1

• Allelic Composition: Esrrb^tm1.1Nat/Esrrb^tm1.1Nat; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6N * FVB/N

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

mortality/aging

premature death ( J:241078 )

• poor survival rates after 9-10 months of age

cardiovascular system

enlarged heart ( J:241078 )

• increase in heart weight to body weight and heart weight to tibial length ratios

dilated heart left ventricle ( J:241078 )

cardiac fibrosis ( J:241078 )

• increase in fibrosis in the left ventricle

dilated cardiomyopathy ( J:241078 )

• mice develop adult-onset dilated cardiomyopathy associated with a decrease in anterior wall thickness, increased left ventricular end systolic diameter and left ventricular end diastolic diameter and a 60% decrease in fractional shortening

decreased cardiac muscle contractility ( J:241078 )

• decrease in cardiac function at 9 months of age but not at 4 and 6 months, with a 60% decrease in fractional shortening

decreased ventricle muscle contractility ( J:241078 )

• ventricular cardiomyocytes exhibit impaired contractility and show a decrease in both contractile distance (sarcomere shortening) and speed of contraction at 6 and 9 months of age

abnormal myocardial fiber physiology ( J:241078 )

• ventricular cardiomyocytes exhibit impaired calcium handling and deregulation of the excitation-contraction coupling apparatus

decreased calcium uptake by cardiac muscle ( J:241078 )

• ventricular cardiomyocytes exhibit decreased calcium release and a trend towards decreased calcium uptake as early as 4 months of age

increased calcium uptake by cardiac muscle ( J:241078 )

• by 6 months of age, calcium release and uptake by ventricular cardiomyocytes are increased and this persists at 9 months

• increase in calcium transients at 6 and 9 months of age

congestive heart failure ( J:241078 )

• expression analysis indicates a heart failure gene signature in hearts

muscle

dilated cardiomyopathy ( J:241078 )

• mice develop adult-onset dilated cardiomyopathy associated with a decrease in anterior wall thickness, increased left ventricular end systolic diameter and left ventricular end diastolic diameter and a 60% decrease in fractional shortening

decreased cardiac muscle contractility ( J:241078 )

• decrease in cardiac function at 9 months of age but not at 4 and 6 months, with a 60% decrease in fractional shortening

decreased ventricle muscle contractility ( J:241078 )

• ventricular cardiomyocytes exhibit impaired contractility and show a decrease in both contractile distance (sarcomere shortening) and speed of contraction at 6 and 9 months of age

abnormal sarcomere morphology ( J:241078 )

• ventricular cardiomyocytes exhibit an increase in sarcomere length only after 9 months of age

growth/size/body

enlarged heart ( J:241078 )

• increase in heart weight to body weight and heart weight to tibial length ratios

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:241078

Genotype
MGI:3723508

cn2

• Allelic Composition: Esrrb^tm1.1Nat/Esrrb^tm1.2Nat; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL

behavior/neurological

absent startle reflex ( J:124941 )

• no auditory startle reflex

head bobbing ( J:124941 )

• observed beginning at several weeks of age

circling ( J:124941 )

• adults spin or run in circles

hearing/vestibular/ear

abnormal scala media morphology ( J:124941 )

• collapsed at 7 days of age

small scala media ( J:124941 )

• reduction in volume seen at 4 days of age

abnormal semicircular canal morphology ( J:124941 )

• narrowing of membranous labyrinths of the three semicircular canals is observed in postnatal animals

abnormal semicircular canal ampulla morphology ( J:124941 )

• flattening of ampullae is observed postnatally

decreased endolymph production ( J:124941 )

increased or absent threshold for auditory brainstem response ( J:124941 )

Genotype
MGI:3723507

cn3

• Allelic Composition: Esrrb^tm1.1Nat/Esrrb^tm1.2Nat; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

hearing/vestibular/ear

absent strial marginal cells ( J:124941 )

• loss of strial margenial cells in mutants is observed; this leads to loss of intraepithelial capillaries

increased or absent threshold for auditory brainstem response ( J:124941 )

• ABR thresholds are variably elevated between 1 and 3 months of age