Phenotypes associated with this allele

• Allele Symbol: Atp2b1^tm1.1Raku
• Allele Name: targeted mutation 1.1, Rajiv Kumar
• Allele ID: MGI:5888894
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Atp2b1^tm1.1Raku/Atp2b1^tm1.1Raku Tg(Vil1-cre)997Gum/0	involves: C57BL/6 * C57BL/6J	MGI:5904968
cn2	Atp2b1^tm1.1Raku/Atp2b1^tm1.1Raku Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:8317196

Genotype
MGI:5904968

cn1

• Allelic Composition: Atp2b1^tm1.1Raku/Atp2b1^tm1.1Raku; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: C57BL/6 * C57BL/6J

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

mortality/aging

prenatal lethality, incomplete penetrance ( J:232942 )

• mice are born at a lower than the expected 25% Mendelian frequency

growth/size/body

decreased birth body size ( J:232942 )

• mice are smaller than control mice at birth

decreased body size ( J:232942 )

• adult mice are smaller than control mice

skeleton

decreased bone mineral density ( J:232942 )

• at 2 months of age, mice fed a 0.81% calcium, 0.34% phosphorus, normal vitamin D diet show a reduction in whole body bone mineral density relative to control mice

decreased bone mineral density of femur ( J:232942 )

• femoral bone mineral density is reduced relative to than in control mice

decreased bone mineralization ( J:232942 )

• mice exhibit reduced bone mineral deposition

homeostasis/metabolism

decreased urine calcium level ( J:232942 )

• urinary calcium concentrations tend to be lower than those in control mice (P = 0.15)

abnormal urine phosphate level ( J:232942 )

• urinary phosphorus concentrations tend to be lower than those in control mice (P = 0.08)

• the urinary phosphorus concentration normalized for creatinine is higher than that in control mice

digestive/alimentary system

decreased intestinal calcium absorption ( J:232942 )

• following i.p. administration of 1alpha,25(OH)₂D₃, mice fail to show an increase in active intestinal calcium transport in everted gut sacs, unlike similarly treated wild-type controls where a ~2-fold increase is observed

renal/urinary system

decreased urine calcium level ( J:232942 )

• urinary calcium concentrations tend to be lower than those in control mice (P = 0.15)

abnormal urine phosphate level ( J:232942 )

• urinary phosphorus concentrations tend to be lower than those in control mice (P = 0.08)

• the urinary phosphorus concentration normalized for creatinine is higher than that in control mice

Genotype
MGI:8317196

cn2

• Allelic Composition: Atp2b1^tm1.1Raku/Atp2b1^tm1.1Raku; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

cardiovascular system

cardiovascular system phenotype ( J:379832 )

N • isolated adult cardiomyocytes exhibit normal global Ca2+ handling with an amplitude of systolic Ca2+ transient and rate of Ca2+ decay similar to controls, suggesting normal diastolic Ca2+ removal during excitation contraction coupling; no change in the mRNA or protein levels of the plasma membrane Na+/Ca2+ exchanger SLC8A1 (aka NCX1) is observed

N • at 3 months of age, mice exhibit normal heart size (based on heart weight/tibia length ratio) and normal cardiac function (as measured by fractional shortening and left ventricular diameters), with no major change in cardiomyocyte cell size or cardiac fibrosis, indicating absence of structural cardiomyopathy; expression levels of structural components related to cardiac conduction are similar to those in controls

irregular heartbeat ( J:379832 )

• under basal conditions, adult mice show altered cardiac rhythm, as evident by prolonged QT, QTc, and JT intervals

• after S1S2 programmed electrical stimulation (PES) of the ventricular myocardium, hearts show an increased susceptibility to arrhythmic events under both in vivo and ex vivo conditions

• increased vulnerability to arrhythmias is associated with a reduction in the transient outward potassium current (Ito) and proteomic remodeling

ventricular arrhythmia ( J:379832 )

• in vivo, 6 out of 9 mice exhibit pacing induced ventricular arrhythmias after S1S2 PES versus only 1 out of 7 in controls

• ex vivo, 4 out of 7 mice exhibit pacing induced ventricular arrhythmias after S1S2 PES versus 0 (none) out of 4 in controls

ventricular tachycardia ( J:379832 )

• after S1S2 programmed electrical stimulation (PES), mice exhibit significantly more arrhythmic events than controls, usually in the form of sustained ventricular tachycardia

abnormal heart electrocardiography waveform feature ( J:379832 )

• under basal conditions, unconscious in vivo ECG recordings from adult male mice show prolonged QT, QTc, and JT intervals, suggestive of ventricular repolarization changes, with similar results observed in female mice

• under basal conditions, JT interval duration is 21.72 ms versus 9.29 ms in controls

• however, heart rate, QRS complex duration, and the RR and PR intervals are not significantly altered under basal conditions

• conscious in vivo ECG recordings reveal no change in the heart rate or RR interval, suggesting basal functioning of the atria is normal

prolonged QT interval ( J:379832 )

• under basal conditions, QT duration is 32.26 ms versus 19.13 ms in controls

prolonged corrected QT interval ( J:379832 )

• under basal conditions, corrected QT duration for heart rate (QTc = QT/(RR/100) is 27.82 ms versus 16.60 ms in controls

abnormal myocardial fiber currents ( J:379832 )

• ventricular mRNA expression of Kcnd2 (potassium voltage-gated channel, Shal-related family, member 2, aka Kv4.2) which contributes to the transient outward K+ current (Ito) involved in ventricular repolarization is significantly decreased; mRNA levels of Kchip2 and Scn1b, known regulators of Kv4.2/Kv4.3 and Ito, are also altered relative to controls

• isolated ventricular cardiomyocytes show a significant reduction in the Ito current both at the peak current and during steady state relative to controls

• however, mRNA expression levels of Scn5a (sodium channel, voltage-gated, type V, alpha, aka Nav1.5; involved in cardiac depolarization) and Cacna1c (calcium channel, voltage-dependent, L type, alpha 1C subunit; involved in cardiac contraction) remain unchanged

nervous system

abnormal action potential ( J:379832 )

• ex vivo, Langendorff-perfused hearts show significantly longer ventricular action potential durations (APD), as evident by APD50 (50% repolarization (APD50) and APD90 (90% repolarization) measurements, complimenting the prolonged QT and JT intervals observed in vivo

muscle

abnormal myocardial fiber currents ( J:379832 )

• ventricular mRNA expression of Kcnd2 (potassium voltage-gated channel, Shal-related family, member 2, aka Kv4.2) which contributes to the transient outward K+ current (Ito) involved in ventricular repolarization is significantly decreased; mRNA levels of Kchip2 and Scn1b, known regulators of Kv4.2/Kv4.3 and Ito, are also altered relative to controls

• isolated ventricular cardiomyocytes show a significant reduction in the Ito current both at the peak current and during steady state relative to controls

• however, mRNA expression levels of Scn5a (sodium channel, voltage-gated, type V, alpha, aka Nav1.5; involved in cardiac depolarization) and Cacna1c (calcium channel, voltage-dependent, L type, alpha 1C subunit; involved in cardiac contraction) remain unchanged

behavior/neurological

behavior/neurological phenotype ( J:379832 )

N • adult mice are overtly normal and behaviorally indistinguishable from control littermates