Phenotypes associated with this allele

• Allele Symbol: Atp2a2^tm1Fwuy
• Allele Name: targeted mutation 1, Frank Wuytack
• Allele ID: MGI:3653502
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Atp2a2^tm1Fwuy/Atp2a2^tm1Fwuy	involves: 129S1/Sv * 129X1/SvJ * Swiss	MGI:3656473
cx2	Atp2a2^tm1Fwuy/Atp2a2^tm1Fwuy Pln^tm1Egk/Pln^tm1Egk	involves: 129 * FVB/N * Swiss	MGI:3662928

Genotype
MGI:3656473

hm1

• Allelic Composition: Atp2a2^tm1Fwuy/Atp2a2^tm1Fwuy
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Swiss

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

mortality/aging

neonatal lethality, incomplete penetrance ( J:111247 )

• 18% of newborn homozygous mutant mice died within the first 4 days after birth (most of them at P0 or P1)

• premature death due to malfunctioning of the neonatal heart from hypoplastic left heart syndrome

• homozygous mice that survived the first postnatal days developed to adulthood

prenatal lethality, incomplete penetrance ( J:111247 )

• significantly lower than expected ratio of mutant homozygous at weaning, indicating some embryonic and/or neonatal lethality

• number of intrauterine resorptions are increased at day E12.5 an E14.5 in homozygous mice compared to wild-type

cardiovascular system

ascending aorta hypoplasia ( J:111247 )

• hypoplasia of the ascending aorta in preterminal mice between P0 to P4

aorta coarctation ( J:111247 )

• of the ascending aorta in preterminal mice between P0 to P4

thin ventricle myocardium compact layer ( J:111247 )

• homozygous embryonic hearts at E12.5 to E14.5 were hypoplastic with a thinner compact layer of the ventricular wall

atrial septal defect ( J:111247 )

• in preterminal mice between P0 to P4

increased heart left ventricle septal wall thickness ( J:111247 )

• adult hearts showed increased left ventricular septal wall thickness compared to wild-type

ventricular septal defect ( J:111247 )

• in preterminal mice between P0 to P4

globular heart ( J:111247 )

• marked reduction in the long axes and loss of the normal ellipsoid form in the adult heart, in favor of a more spherical appearance

increased heart weight ( J:111247 )

• in adult homozygous mice, heart weight/body weight ratios are increased compared to wild-type

cardiac hypertrophy ( J:111247 )

• in adult homozygous mice, histological section of hearts showed overall myocyte organization consistent with concentric hypertrophy

heart left ventricle hypertrophy ( J:111247 )

• in preterminal mice between P0 to P4

increased heart left ventricle posterior wall thickness ( J:111247 )

• adult hearts showed increased left ventricular posterior wall thickness compared to wild-type

dilated heart right ventricle ( J:111247 )

• in preterminal mice between P0 to P4

cardiac fibrosis ( J:111247 )

• fibrosis in the atrium in preterminal mice between P0 to P4

cardiac interstitial fibrosis ( J:111247 )

• in adult homozygous mice, histological section of hearts showed excessive interstitial fibrosis

decreased cardiac muscle contractility ( J:111247 )

• rate of contraction was significantly depressed in adult homozygous mice

• absolute values of +dP/dt was significantly lower in adult homozygous mice under basal condition and at all level of beta-adrenergic stimulation

• time to peak pressure and half relaxation time were prolonged in adult homozygous mice

abnormal cardiac muscle relaxation ( J:111247 )

• rate of relaxation was significantly depressed in adult homozygous mice

• absolute values of -dP/dt was significantly lower in adult homozygous mice under basal condition and at all level of beta-adrenergic stimulation

• time to peak pressure and half relaxation time were prolonged in adult homozygous mice

muscle

thin ventricle myocardium compact layer ( J:111247 )

• homozygous embryonic hearts at E12.5 to E14.5 were hypoplastic with a thinner compact layer of the ventricular wall

heart left ventricle hypertrophy ( J:111247 )

• in preterminal mice between P0 to P4

decreased cardiac muscle contractility ( J:111247 )

• rate of contraction was significantly depressed in adult homozygous mice

• absolute values of +dP/dt was significantly lower in adult homozygous mice under basal condition and at all level of beta-adrenergic stimulation

• time to peak pressure and half relaxation time were prolonged in adult homozygous mice

abnormal cardiac muscle relaxation ( J:111247 )

• rate of relaxation was significantly depressed in adult homozygous mice

• absolute values of -dP/dt was significantly lower in adult homozygous mice under basal condition and at all level of beta-adrenergic stimulation

• time to peak pressure and half relaxation time were prolonged in adult homozygous mice

homeostasis/metabolism

abnormal calcium ion homeostasis ( J:111247 )

• the maximum rate of ATP-dependent oxalate-facilitated calcium ion uptake was significantly reduced in cardiac homogenates of homozygous mice

• rate of calcium ion removal by the sarcoplasmic reticulum was reduced in isolated ventricular myocyte from homozygous mice

behavior/neurological

impaired righting response ( J:111247 )

• in preterminal mice between P0 to P4

abnormal locomotor activation ( J:111247 )

• markedly reduced spontaneous nocturnal activity in a treadmill test in homozygous surviving to adult

• homozygous mice surviving to adult are fertile

bradykinesia ( J:111247 )

• striking sluggishness of their movements in preterminal mice between P0 to P4

fatigue ( J:111247 )

• in preterminal mice between P0 to P4

growth/size/body

increased heart weight ( J:111247 )

• in adult homozygous mice, heart weight/body weight ratios are increased compared to wild-type

cardiac hypertrophy ( J:111247 )

• in adult homozygous mice, histological section of hearts showed overall myocyte organization consistent with concentric hypertrophy

heart left ventricle hypertrophy ( J:111247 )

• in preterminal mice between P0 to P4

decreased body weight ( J:111247 )

• preterminal mice between P0 to P4 showed a lower body weight and lack of milk consumption

reproductive system

decreased litter size ( J:111247 )

• average litter size obtained at birth for homozygous mice we 20% lower than wild-type

cellular

cardiac interstitial fibrosis ( J:111247 )

• in adult homozygous mice, histological section of hearts showed excessive interstitial fibrosis

Genotype
MGI:3662928

cx2

• Allelic Composition: Atp2a2^tm1Fwuy/Atp2a2^tm1Fwuy; Pln^tm1Egk/Pln^tm1Egk
• Genetic Background: involves: 129 * FVB/N * Swiss

growth/size/body

increased heart weight ( J:110974 )

• in double homozygous mice, heart weight/body weight ratios and heart weight/tibial length ratios are increased compared to wild-type

cardiac hypertrophy ( J:110974 )

• in double homozygous mice at 12-16 weeks, concentric hypertrophy was aggravated compared to single Atp2a2^tm1Fwuy homozygous mice

mortality/aging

premature death ( J:110974 )

• the life span of mutant mice was severely shortened at 496 average age in days

cardiovascular system

increased myocardial fiber size ( J:110974 )

• the cardiomyocyte dimensions in double homozygous mice were increased to a much larger extent than in single Atp2a2^tm1Fwuy homozygous mice

globular heart ( J:110974 )

• the hearts from double homozygous mice were more hypertrophic and balloon-shaped than the heart from single Atp2a2^tm1Fwuy homozygous mice

increased heart weight ( J:110974 )

• in double homozygous mice, heart weight/body weight ratios and heart weight/tibial length ratios are increased compared to wild-type

cardiac hypertrophy ( J:110974 )

• in double homozygous mice at 12-16 weeks, concentric hypertrophy was aggravated compared to single Atp2a2^tm1Fwuy homozygous mice

thick ventricular wall ( J:110974 )

• in double homozygous mice at 12-16 weeks, echocardiographic measurements showed thicker posterior wall than single Atp2a2^tm1Fwuy homozygous mice

increased heart left ventricle wall thickness ( J:110974 )

• cardiac sections showed a larger LV mass-measured as cross-sectional area

• LV wall thickening was not the result of increased interstitial fibrosis

abnormal cardiac output ( J:110974 )

• beta-adrenergic stimulation in double homozygous mice failed to increase the cardiac output

decreased cardiac stroke volume ( J:110974 )

• maximal and minimal LV volume and stroke volume appeared lower in double homozygous mice at 12-16 weeks

abnormal cardiac muscle relaxation ( J:110974 )

• impaired LV relaxation assessed by dP/dt min in double homozygous mice at 12-16 weeks compared to wild-type mice

• contractility assessed by dP/dt max were normal

decreased heart rate ( J:110974 )

• in double homozygous mice at 12-16 weeks compared to wild-type

congestive heart failure ( J:110974 )

• two out of 16 double homozygous mice died after completing running performance test on a rodent treadmill displaying clinical signs of congestive heart failure

• beta-adrenergic stimulation impaired LV contractility and relaxation and caused acute heart failure during the procedure

behavior/neurological

abnormal locomotor activation ( J:110974 )

• the spontaneous activity was severely reduced in double homozygous mice at 12-16 weeks of age compared to wild-type and single Atp2a2^tm1Fwuy homozygous mice

homeostasis/metabolism

abnormal calcium ion homeostasis ( J:110974 )

• the maximal pumping capacity of sarcoplasmic reticulum calcium ion uptake was reduced by 50% in cardiac homogenate of homozygous mutant mice

muscle

increased myocardial fiber size ( J:110974 )

• the cardiomyocyte dimensions in double homozygous mice were increased to a much larger extent than in single Atp2a2^tm1Fwuy homozygous mice

abnormal cardiac muscle relaxation ( J:110974 )

• impaired LV relaxation assessed by dP/dt min in double homozygous mice at 12-16 weeks compared to wild-type mice

• contractility assessed by dP/dt max were normal