All Phenotypes Xirp2<tm1Jl> MGI Mouse

postnatal lethality, complete penetrance ( J:158491 )

• from P3.5 and on, the number of viable mice is significantly lower than expected

• all die before weaning

decreased birth weight ( J:158491 )

• about 14% lighter at P0.5

decreased body weight ( J:158491 )

• by P12.5 mice weigh about 45% of controls

postnatal growth retardation ( J:158491 )

slow postnatal weight gain ( J:158491 )

• between birth and P12.5 mice gain weight slower than wild-type

decreased locomotor activity ( J:158491 )

• reduced activity

abnormal Purkinje fiber morphology ( J:255706 )

• at P18, acetylcholine esterase (AChE) staining performed on serial sections of entire hearts revealed a reduction in Purkinje fibers

abnormal atrioventricular bundle morphology ( J:255706 )

• at P18, hearts exhibit reduced expression of connexin 40 (Cx40, a major gap junction protein of the His-bundle and bundle branches ) in the His-bundle compared to wild-type hearts

abnormal myocardial fiber morphology ( J:158491 )

• by P12.5 cardiomyocytes became more irregularly shaped

abnormal intercalated disk morphology ( J:158491 )

• a defect in the maturation of intercalated discs, by EM the membranes at the maturing intercalated discs are less convoluted and less wavy

decreased myocardial fiber size ( J:158491 )

• by P12.5 cardiomyocytes became smaller in cell width

abnormal trabecula carnea morphology ( J:158491 )

• a nonsignificant trend of an increase in the area of left and right ventricle trabecular myocardium compared to wild-type

ventricular myocardium compact layer hypoplasia ( J:158491 )

• a significant reduction in the area of left and right ventricle compact myocardium

disorganized myocardium ( J:158491 )

• noncompaction in right ventricle could be detected at E14.5

muscular ventricular septal defect ( J:158491 )

• septal defect in 58% of mice at birth

• defects could be small, large or multiple and found in any location within the muscular septum

abnormal heart shape ( J:158491 )

• in 15% of mice at birth

decreased heart weight ( J:158491 )

• at P7.5 and P12.5 wild-type hearts are significantly larger

• however, the heart weight to body weight ratio is increased

abnormal heart left ventricle morphology ( J:158491 )

• a reduction in left ventricular internal dimension and volume in both P3.5 and P12 mice during diastole and systole

• a significant reduction in the area of left ventricle compact myocardium and a nonsignificant trend of an increase in the area of left ventricle trabecular myocardium compared to wild-type

abnormal heart right ventricle morphology ( J:158491 )

• trend of decrease in compact area and increase in trabecular area were also observed for right ventricle

abnormal cardiovascular system physiology ( J:158491 )

• at P7.5 mutant hearts show slightly reduced cell proliferation

decreased diastolic filling velocity ( J:158491 )

• exhibit abnormal ventricular filling

• mitral inflow E-wave (early filling) but not A-wave (atrial contraction) peak velocity is reduced

• E/A ratios are also significantly smaller

abnormal impulse conducting system conduction ( J:255706 )

• mice surviving to P20 exhibit a 45% reduction in conduction velocity in left ventricles compared to wild-type controls

• optical mapping revealed that ventricles exhibit slow action potential (AP) propagation

atrioventricular block ( J:255706 )

• at P18, all tested mice show a severe atrioventricular conduction (A-V) block with many P waves followed by missing QRS wave

prolonged PR interval ( J:255706 )

• at P14-P17, mice show a significantly prolonged PR interval

abnormal heart electrocardiography waveform feature ( J:255706 )

• at P14-P17, mice show a significantly prolonged PR interval and prolonged QT and QTc intervals, but no changes in P wave and QRS interval, suggesting a defect in the infranodal ventricular conduction system

• ventricular myocytes exhibit altered action potential (AP) waveforms, with significantly increased AP amplitude, less negative maximal diastolic potential, and shorter APD at 20%, 50%, and 90% repolarization levels

prolonged QT interval ( J:255706 )

• at P14-P17, mice show prolonged QT and QTc intervals

abnormal myocardial fiber currents ( J:255706 )

• isolated ventricular myocytes exhibit depressed transient outward K⁺ (I_TO) currents and current densities at pulsed voltages from +20 to +60 mV

• the amplitudes and current densities of the outward delayed rectifier K⁺ current (I_K) are significantly increased

• the amplitudes and current densities of the Ba²⁺-sensitive inward rectifier K⁺ current (I_K1) are significantly increased at negative voltage from -70 to -120 mV

• however, the inward Na⁺ current (I_Na) current densities are relatively normal

decreased liver weight ( J:158491 )

• liver weight is significantly reduced between P3.5 and P7.5

• however, the liver weight to body weight ratio is not different than wild-type