Phenotypes Associated with This Genotype

Genotype
MGI:5910053

• Allelic Composition: Tg(Myh6-TNNT2*I79N)8Jdp/0
• Genetic Background: involves: C57BL/6 * SJL

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

cardiovascular system

abnormal heart morphology ( J:213305 )

• mice challenged with isoproterenol exhibit altered cardiac gap junctions

• rapid pacing of isolated hearts induces changes in connexin 43 protein expression, solubility, and isoform distribution and results in accumulation of dephosphorylated connexin 43 isoform P0 in cardiac tissue

• cardiac tissue after isoproterenol challenge shows a reduction in junctional connexin 43 and regions of connexin 43 isoform P0 accumulation

decreased heart weight ( J:67284 )

• small decrease in heart weight to body weight ratio

• mice do not exhibit cardiac hypertrophy

abnormal cardiovascular system physiology ( J:213305 )

• rapid pacing of isolated hearts increases anisotropy ratio, with transverse conduction velocity reduced by more than 20%

• after rapid pacing challenge, the myocardium, in areas of connexin 43 isoform P0 accumulation, is energetically compromised as indicated by an increase in activated AMP-dependent kinase in these areas resulting in ATP depletion

• following pacing, Lucifer yellow dye spread through intact cardiomyocytes is reduced indicating reduced gap junctional intercellular coupling

ventricular tachycardia ( J:213305 )

• 25% of mice challenged with the catecholamine isoproterenol exhibit ventricular tachycardia

• rapid pacing of isolated hearts induces ventricular tachycardia in more than 50% of mice

ventricular premature beat ( J:213305 )

• 56% of mice challenged with the catecholamine isoproterenol exhibit ventricular ectopy

prolonged QRS complex duration ( J:213305 )

• mice treated with isoproterenol exhibit progressive prolongation of QRS duration

• rapid pacing of isolated hearts causes progressive QRS prolongation

abnormal myocardial fiber physiology ( J:67284 )

• papillary muscle fibers exhibit increased calcium sensitivity of steady state force development in both sedentary and exercised groups

• maximal steady state force developed by muscle fibers is decreased in both sedentary and exercised groups

• muscle fibers show an increased rate of force activation and moderately increased rate of relaxation

• cardiac muscle is less sensitive to acidic pH and shows a smaller decrease in calcium-sensitivity of force development indicating a loss of sensitivity to pH-induced shifts in calcium dependence of force

• large increase in the calcium sensitivity of the ATPase activity and force development in skinned fibers

mortality/aging

mortality/aging ( J:67284 )

N • mice exhibit normal survival and chronic swimming exercises do not affect survival

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 2		DOID:0110308	OMIM:115195	J:213305