Phenotypes associated with this allele

• Allele Symbol: Cacna1c^tm2.1Wac
• Allele Name: targeted mutation 2.1, William A Catterall
• Allele ID: MGI:5662550
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacna1c^tm2.1Wac/Cacna1c^tm2.1Wac	involves: C57BL/6	MGI:5771663

Genotype
MGI:5771663

hm1

• Allelic Composition: Cacna1c^tm2.1Wac/Cacna1c^tm2.1Wac
• Genetic Background: involves: C57BL/6

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

cardiovascular system

increased heart weight ( J:216746 )

• 26% increase in heart/body-weight ratio by 3-4 months of age

cardiac hypertrophy ( J:216746 )

• by 3-4 months of age, homozygotes develop cardiac hypertrophy, as shown by a 26% increase in heart/body-weight ratio and a 15% increase in cellular hypertrophy measured as cell-surface capacitance relative to wild-type controls

• homozygotes are overtly normal prior to P60

decreased cardiac muscle contractility ( J:216746 )

• in vitro, cell shortening induced by isoproterenol treatment is not significantly altered in dissociated myocytes, except at 10 nM, where it is reduced by 30% relative to wild-type controls

• no episodes of isoproterenol-induced asynchronous contractions or contraction failures are observed, indicating a mild deficit in myocyte contractility

abnormal fetal cardiomyocyte physiology ( J:216746 )

• dissociated neonatal cardiomyocytes (P0-P2) show significantly reduced basal L-type Ca²⁺ channel activity relative to wild-type cardiomyocytes (peak L-type current at +10 mV is 268 +/- 38 pA vs 419 +/- 55 pA, respectively)

• response to beta-adrenergic activation by 1 uM isoproterenol is blunted in neonatal cardiomyocytes

abnormal myocardial fiber physiology ( J:216746 )

• adult ventricular myocytes show a reduction in basal L-type Ca²⁺ current to ~37% of the wild-type value

• marked reduction in peak Ca²⁺ current amplitude in response to 3, 10, and 100 nM isoproterenol relative to wild-type controls

• full beta-adrenergic activation by maximal stimulation with 100 nM isoproterenol increases Ca²⁺ current to only ~33% of the wild-type value

decreased calcium uptake by cardiac muscle ( J:216746 )

• reduced Ca²⁺ entry into cardiomyocytes

homeostasis/metabolism

decreased aerobic running capacity ( J:216746 )

• when forced to run uphill on a treadmill to escape a foot shock, homozygotes show a 30% decrease in total running distance before exhaustion relative to wild-type controls

abnormal calcium ion homeostasis ( J:216746 )

• reduction in basal and beta-adrenergic stimulated calcium currents leading to impaired cardiovascular physiology

behavior/neurological

decreased aerobic running capacity ( J:216746 )

• when forced to run uphill on a treadmill to escape a foot shock, homozygotes show a 30% decrease in total running distance before exhaustion relative to wild-type controls

muscle

decreased cardiac muscle contractility ( J:216746 )

• in vitro, cell shortening induced by isoproterenol treatment is not significantly altered in dissociated myocytes, except at 10 nM, where it is reduced by 30% relative to wild-type controls

• no episodes of isoproterenol-induced asynchronous contractions or contraction failures are observed, indicating a mild deficit in myocyte contractility

growth/size/body

increased heart weight ( J:216746 )

• 26% increase in heart/body-weight ratio by 3-4 months of age

cardiac hypertrophy ( J:216746 )

• by 3-4 months of age, homozygotes develop cardiac hypertrophy, as shown by a 26% increase in heart/body-weight ratio and a 15% increase in cellular hypertrophy measured as cell-surface capacitance relative to wild-type controls

• homozygotes are overtly normal prior to P60