Phenotypes associated with this allele

• Allele Symbol: Tg(Myh6-CASQ2)1Mord
• Allele Name: transgene insertion 1, Martin Morad
• Allele ID: MGI:2389055
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Hrtfm4^AKR/J/Hrtfm4^AKR/J Tg(Myh6-CASQ2)1Mord/0	involves: AKR/J * DBA/2J	MGI:2686965
cx2	Hrtfm5^AKR/J/? Tg(Myh6-CASQ2)1Mord/0	involves: AKR/J * DBA/2J	MGI:2686966
cx3	Hrtfm6^AKR/J/? Tg(Myh6-CASQ2)1Mord/0	involves: AKR/J * DBA/2J	MGI:2686968
cx4	Tg(Myh6-CASQ2)1Mord/0 Tnni3k^B/Tnni3k^A	involves: AKR/J * DBA/2J	MGI:7540821
cx5	Tg(Myh6-CASQ2)1Mord/0 Tnni3k^B/Tnni3k^B	involves: AKR/J * DBA/2J	MGI:7540830
cx6	Hrtfm3^AKR/J/Hrtfm3^AKR/J Tg(Myh6-CASQ2)1Mord/0	involves: AKR/J * DBA/2J	MGI:2686963
cx7	Tg(Myh6-CASQ2)1Mord/0 Tg(Myh6-TNNI3K)#Dmar/0 Tnni3k^B/Tnni3k^B	involves: C57BL/6J * DBA/2J * SJL/J	MGI:7540832
tg8	Tg(Myh6-CASQ2)1Mord/0	Not Specified	MGI:3700949

Genotype
MGI:2686965

cx1

• Allelic Composition: Hrtfm4^AKR/J/Hrtfm4^AKR/J; Tg(Myh6-CASQ2)1Mord/0
• Genetic Background: involves: AKR/J * DBA/2J

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

mortality/aging

extended life span ( J:86767 )

• increased survival

cardiovascular system

dilated cardiomyopathy ( J:86767 )

• improved echocardiographic fractional shortening versus transgenic mice homozygous for Hrtfm4^DBA/2J

muscle

dilated cardiomyopathy ( J:86767 )

• improved echocardiographic fractional shortening versus transgenic mice homozygous for Hrtfm4^DBA/2J

Genotype
MGI:2686966

cx2

• Allelic Composition: Hrtfm5^AKR/J/?; Tg(Myh6-CASQ2)1Mord/0
• Genetic Background: involves: AKR/J * DBA/2J

cardiovascular system

dilated cardiomyopathy ( J:86767 )

• mice with the transgene and at least one AKR/J allele at Hrtfm5 exhibit improved echocardiographic fractional shortening and left ventricular diastolic diameter versus transgenic mice homozygous for Hrtfm5^DBA/2J

muscle

dilated cardiomyopathy ( J:86767 )

• mice with the transgene and at least one AKR/J allele at Hrtfm5 exhibit improved echocardiographic fractional shortening and left ventricular diastolic diameter versus transgenic mice homozygous for Hrtfm5^DBA/2J

Genotype
MGI:2686968

cx3

• Allelic Composition: Hrtfm6^AKR/J/?; Tg(Myh6-CASQ2)1Mord/0
• Genetic Background: involves: AKR/J * DBA/2J

cardiovascular system

dilated cardiomyopathy ( J:86767 )

• mice with the transgene and at least one AKR/J allele at Hrtfm6 exhibit improved fractional shortening and improved left ventricular diastolic diameter versus transgenic mice homozygous for Hrtfm6^DBA/2J

muscle

dilated cardiomyopathy ( J:86767 )

• mice with the transgene and at least one AKR/J allele at Hrtfm6 exhibit improved fractional shortening and improved left ventricular diastolic diameter versus transgenic mice homozygous for Hrtfm6^DBA/2J

Genotype
MGI:7540821

cx4

• Allelic Composition: Tg(Myh6-CASQ2)1Mord/0; Tnni3k^B/Tnni3k^A
• Genetic Background: involves: AKR/J * DBA/2J

cardiovascular system

decreased cardiac muscle contractility ( J:154116 )

• reduced fractional shortening at age 4 and 8 weeks

mortality/aging

extended life span ( J:154116 )

• average 107-day survival (vs 40 days for homozygous Tnni3k (WT) with transgene)

muscle

decreased cardiac muscle contractility ( J:154116 )

• reduced fractional shortening at age 4 and 8 weeks

Genotype
MGI:7540830

cx5

• Allelic Composition: Tg(Myh6-CASQ2)1Mord/0; Tnni3k^B/Tnni3k^B
• Genetic Background: involves: AKR/J * DBA/2J

mortality/aging

extended life span ( J:154116 )

• average 150-day survival (vs 40 days for homozygous Tnni3k (WT) with transgene)

Genotype
MGI:2686963

cx6

• Allelic Composition: Hrtfm3^AKR/J/Hrtfm3^AKR/J; Tg(Myh6-CASQ2)1Mord/0
• Genetic Background: involves: AKR/J * DBA/2J

mortality/aging

extended life span ( J:86767 )

• increased survival versus transgenic mice homozygous for Hrtfm3^DBA/2J

Genotype
MGI:7540832

cx7

• Allelic Composition: Tg(Myh6-CASQ2)1Mord/0; Tg(Myh6-TNNI3K)#Dmar/0; Tnni3k^B/Tnni3k^B
• Genetic Background: involves: C57BL/6J * DBA/2J * SJL/J

cardiovascular system

dilated cardiomyopathy ( J:154116 )

• at around age 14 days

decreased cardiac muscle contractility ( J:154116 )

• reduced fractional shortening at around age 14 days

decreased heart rate ( J:154116 )

• at around age 14 days

mortality/aging

premature death ( J:154116 )

• average 21-day survival (vs 40 days for homozygous Tnni3k (WT) with CASQ2 transgene only)

muscle

dilated cardiomyopathy ( J:154116 )

• at around age 14 days

decreased cardiac muscle contractility ( J:154116 )

• reduced fractional shortening at around age 14 days

Genotype
MGI:3700949

tg8

• Allelic Composition: Tg(Myh6-CASQ2)1Mord/0
• Genetic Background: Not Specified

mortality/aging

premature death ( J:79838 )

• all mice die by 16 weeks of age

cardiovascular system

abnormal heart morphology ( J:79838 )

• at 7 and 14 weeks of age, total beta-adrenergic receptor density and the number of high affinity receptors are reduced in hearts

abnormal myocardial fiber morphology ( J:46786 )

• myocytes are filled with a large number of membrane-limited vesicles which pervade the entire cell outline, displacing myofibrils and mitochondria

increased myocardial fiber size ( J:46786 )

• ventricular myocytes are larger and have a distinctive appearance with blurred striations

enlarged heart ( J:79838 )

• mice show mild chamber enlargement at 7 weeks of age and severe cardiac enlargement at 14 weeks of age

cardiac hypertrophy ( J:46786 , J:79838 )

• severe hypertrophy, with a 2-fold increase in heart mass and cell size (J:46786)

• mice initially exhibit cardiac hypertrophy (J:79838)

abnormal heart left ventricle morphology ( J:79838 )

• progressive increase in left ventricular mass from 7 to 14 weeks of age

thick ventricular wall ( J:79838 )

• left ventricular wall thickness is increased at 7 weeks of age but at 14 weeks, wall thickness is reduced to normal values

cardiac fibrosis ( J:46786 )

• cardiac hypertrophy is accompanied by focal areas of fibrosis

dilated cardiomyopathy ( J:79838 )

• mice initially exhibit cardiac hypertrophy with only a mild reduction in systolic function that progresses to severe cardiac enlargement and left ventricular dysfunction with premature death

decreased cardiac muscle contractility ( J:79838 )

• mice show progressive deterioration of cardiac function, showing an increase in left ventricular end-diastolic diameter, a decrease in % fractional shortening, and reduction in wall thickness from 7 to 14 weeks

decreased heart ventricle muscle contractility ( J:79838 )

• hearts of 7 week old mice show a blunted response to isoproterenol

decreased heart left ventricle muscle contractility ( J:79838 )

• first derivative of left ventricular pressure rise (LV dP/dt max) is reduced in 7 week old mice, indicating decreased basal contractility

• mice undergoing right atrial pacing to match heart rate to that of wild-type mice do not exhibit an increase in left ventricular dP/dt max but instead a decline

decreased cardiac muscle relaxation ( J:79838 )

• myocardial relaxation assessed by LV dP/dt min is impaired in 7 and 14 week old mice under basal conditions

abnormal heart echocardiography feature ( J:79838 )

• echocardiography indicates increased wall thickness progressing to left ventricular enlargement and severe cardiac dysfunction

decreased left ventricle systolic pressure ( J:79838 )

• left ventricular systolic pressure is only slightly reduced in 7 week old mice and is reduced in 14 week old mice

decreased heart rate ( J:79838 )

• heart rate is lower at base line and with isoproterenol in 7 and 14 week old mice

increased heart rate ( J:46786 )

• cardiac hypertrophy is accompanied by rapid heart rate

abnormal myocardial fiber physiology ( J:46786 )

• in whole cell-clamped myocytes, calcium-channel-gated calcium release from the sarcoplasmic reticulum is suppressed, the frequency of occurrence of spontaneous or calcium current-triggered 'calcium-sparks' is reduced and the spark perimeter is less defined

• caffeine-induced calcium transients and the resultant sodium-calcium exchanger currents are increased 10-fold in myocytes

homeostasis/metabolism

abnormal fluid regulation ( J:46786 )

• fluid retention

abnormal calcium ion homeostasis ( J:46786 )

• in whole cell-clamped myocytes, calcium-channel-gated calcium release from the sarcoplasmic reticulum is suppressed, the frequency of occurrence of spontaneous or calcium current-triggered 'calcium-sparks' is reduced and the spark perimeter is less defined

respiratory system

abnormal respiration ( J:46786 )

• increase in the respiratory rate

muscle

abnormal myocardial fiber morphology ( J:46786 )

• myocytes are filled with a large number of membrane-limited vesicles which pervade the entire cell outline, displacing myofibrils and mitochondria

increased myocardial fiber size ( J:46786 )

• ventricular myocytes are larger and have a distinctive appearance with blurred striations

dilated cardiomyopathy ( J:79838 )

• mice initially exhibit cardiac hypertrophy with only a mild reduction in systolic function that progresses to severe cardiac enlargement and left ventricular dysfunction with premature death

decreased cardiac muscle contractility ( J:79838 )

• mice show progressive deterioration of cardiac function, showing an increase in left ventricular end-diastolic diameter, a decrease in % fractional shortening, and reduction in wall thickness from 7 to 14 weeks

decreased heart ventricle muscle contractility ( J:79838 )

• hearts of 7 week old mice show a blunted response to isoproterenol

decreased heart left ventricle muscle contractility ( J:79838 )

• first derivative of left ventricular pressure rise (LV dP/dt max) is reduced in 7 week old mice, indicating decreased basal contractility

• mice undergoing right atrial pacing to match heart rate to that of wild-type mice do not exhibit an increase in left ventricular dP/dt max but instead a decline

decreased cardiac muscle relaxation ( J:79838 )

• myocardial relaxation assessed by LV dP/dt min is impaired in 7 and 14 week old mice under basal conditions

abnormal sarcoplasmic reticulum morphology ( J:46786 )

• junctions between the sarcoplasmic reticulum and the surface membrane, or peripheral couplings, and between the sarcoplasmic reticulum and T tubules are less frequent than in wild-type myocardium

• the junctions are smaller and the junctional sarcoplasmic reticulum is enlarged and the calsequestrin content is more dispersed

growth/size/body

enlarged heart ( J:79838 )

• mice show mild chamber enlargement at 7 weeks of age and severe cardiac enlargement at 14 weeks of age

cardiac hypertrophy ( J:46786 , J:79838 )

• severe hypertrophy, with a 2-fold increase in heart mass and cell size (J:46786)

• mice initially exhibit cardiac hypertrophy (J:79838)

cellular

abnormal sarcoplasmic reticulum morphology ( J:46786 )

• junctions between the sarcoplasmic reticulum and the surface membrane, or peripheral couplings, and between the sarcoplasmic reticulum and T tubules are less frequent than in wild-type myocardium

• the junctions are smaller and the junctional sarcoplasmic reticulum is enlarged and the calsequestrin content is more dispersed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:79838