Phenotypes associated with this allele

• Allele Symbol: Tg(Myh6-Tmod1)65Msus
• Allele Name: transgene insertion 65, Mark A Sussman
• Allele ID: MGI:3622294
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Hspb7^tm1.2Chen/Hspb7^tm1.2Chen Tg(Myh6-Tmod1)65Msus/Tg(Myh6-Tmod1)65Msus	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * FVB/N	MGI:6159014
tg2	Tg(Myh6-Tmod1)65Msus/Tg(Myh6-Tmod1)65Msus	FVB/N-Tg(Myh6-Tmod1)65Msus	MGI:3622305
tg3	Tg(Myh6-Tmod1)65Msus/Tg(Myh6-Tmod1)65Msus	involves: FVB/N	MGI:3622299

Genotype
MGI:6159014

cx1

• Allelic Composition: Hspb7^tm1.2Chen/Hspb7^tm1.2Chen; Tg(Myh6-Tmod1)65Msus/Tg(Myh6-Tmod1)65Msus
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * FVB/N

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

HSPB7 represses formation of abnormal actin bundles independent of Tmod1

cardiovascular system

abnormal fetal cardiomyocyte morphology ( J:256653 )

• at E10.5, average thin filament length was comparable to that observed in cardiomyocytes of single Hspb7^tm1.2Chen homozygotes

muscle

abnormal sarcomere morphology ( J:256653 )

• at E10.5, cardiomyocyte sarcomeres exhibited abnormal actin bundles (AABs) and an average thin filament length that was comparable to that observed in cardiomyocytes of single Hspb7^tm1.2Chen homozygotes, indicating that increasing Tmod1 at pointed ends could not rescue either the AAB or longer thin filament phenotype

Genotype
MGI:3622305

tg2

• Allelic Composition: Tg(Myh6-Tmod1)65Msus/Tg(Myh6-Tmod1)65Msus
• Genetic Background: FVB/N-Tg(Myh6-Tmod1)65Msus

mortality/aging

lethality at weaning, incomplete penetrance ( J:58879 )

• first wave of increased mortality occurs around 15-16 days after birth and the second wave at around 21 days of age, with about 50% dying between 14 and 22 days

premature death ( J:58879 )

• 58% die within 6 weeks after birth, although some mutants can live over 1 year

• a third wave of mortality occurs between 30 and 50 days

postnatal lethality, incomplete penetrance ( J:58879 )

• first wave of increased mortality occurs around 15-16 days after birth and the second wave at around 21 days of age, with about 50% dying between 14 and 22 days

• small litters show the highest mortality rates

cardiovascular system

abnormal myocardial fiber morphology ( J:58879 )

• 89% increase in intracellular calcium in cardiomyocytes

• amplitude of the calcium transient is 128% greater than in controls, raising peak systolic calcium level 2-fold above controls

• degenerative changes in sarcomere organization are apparent at birth and by 8 days after birth, show signs of sarcomeric dysgenesis such as poor alignment and wavy appearance

• although Z-disks are present at birth, structures are often poorly spaced or unaligned

increased heart weight ( J:58879 )

• disproportionate increases in heart weight occur around 1.5 weeks after birth, with most of the cardiac enlargement occurring in a very short time of 2-3 days

dilated heart left ventricle ( J:58879 )

• left ventricular chamber increases in size over time (from P11 to P14), however ventricular wall and spetal thickness remain normal at P8, P11 and P14

dilated cardiomyopathy ( J:58879 )

homeostasis/metabolism

anasarca ( J:58879 )

• mortality occurring between 30 and 50 days is associated with the development of anasarca

muscle

abnormal myocardial fiber morphology ( J:58879 )

• 89% increase in intracellular calcium in cardiomyocytes

• amplitude of the calcium transient is 128% greater than in controls, raising peak systolic calcium level 2-fold above controls

• degenerative changes in sarcomere organization are apparent at birth and by 8 days after birth, show signs of sarcomeric dysgenesis such as poor alignment and wavy appearance

• although Z-disks are present at birth, structures are often poorly spaced or unaligned

dilated cardiomyopathy ( J:58879 )

growth/size/body

increased heart weight ( J:58879 )

• disproportionate increases in heart weight occur around 1.5 weeks after birth, with most of the cardiac enlargement occurring in a very short time of 2-3 days

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:58879

Genotype
MGI:3622299

tg3

• Allelic Composition: Tg(Myh6-Tmod1)65Msus/Tg(Myh6-Tmod1)65Msus
• Genetic Background: involves: FVB/N

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:107823 )

• mutants always die if overstressed with physical handling

premature death ( J:107823 )

• mutants with most severe phenotypes show cardiomyopathic changes between 2 and 4 weeks after birth and die within 2-3 days of exhibiting the phenotypes

cardiovascular system

abnormal heart morphology ( J:107823 )

• percentage of cell volume occupied by the nucleus in hearts is significantly greater, however do not exhibit an increase in nuclear number

abnormal myocardial fiber morphology ( J:107823 )

• myofibrils are disorganized, show a loss of parallel alignment, are curved with distorted Z bands, and exhibit sarcomeric dysgenesis, with a 53% reduction in sarcomeric length

• actin and myosin filaments are found without discernible Z bands is some areas, whereas in other regions distinct closely spaced sarcomeres are seen

myocardial fiber degeneration ( J:107823 )

• myofibrils are absent from large areas of the cell and numerous mitochondria are present, consistent with degenerating cardiomyocytes

thin myocardium ( J:107823 )

• the right ventricular myocardial wall is translucent, indicating a decrease in thickness and the left ventricular posterior wall is thinner

increased heart weight ( J:107823 )

abnormal heart ventricle morphology ( J:107823 )

• ventricular wall shows karyomegalic nuclei

thin interventricular septum ( J:107823 )

• thinning of ventricular septum

dilated heart left ventricle ( J:107823 )

• extreme left ventricle dilation despite the thinned myocardium

abnormal cardiovascular system physiology ( J:107823 )

dilated cardiomyopathy ( J:107823 )

• exhibit global dilation with marked right side atrial and ventricular enlargement, however do not exhibit cardiac hypertrophy

decreased cardiac output ( J:107823 )

decreased cardiac muscle contractility ( J:107823 )

• 59% decrease in +dP/dt, indicating reduced contractility

decreased heart left ventricle muscle contractility ( J:107823 )

• left ventricle exhibits decreased shortening fraction and velocity of circumferential fiber shortening

abnormal cardiac muscle relaxation ( J:107823 )

• 52% decrease in -dP/dt, indicating that relaxation is prolonged

decreased heart rate ( J:107823 )

• heart rate is 11% lower than controls

congestive heart failure ( J:107823 )

• some exhibit heart failure at 2-4 weeks of age

muscle

abnormal myocardial fiber morphology ( J:107823 )

• myofibrils are disorganized, show a loss of parallel alignment, are curved with distorted Z bands, and exhibit sarcomeric dysgenesis, with a 53% reduction in sarcomeric length

• actin and myosin filaments are found without discernible Z bands is some areas, whereas in other regions distinct closely spaced sarcomeres are seen

myocardial fiber degeneration ( J:107823 )

• myofibrils are absent from large areas of the cell and numerous mitochondria are present, consistent with degenerating cardiomyocytes

thin myocardium ( J:107823 )

• the right ventricular myocardial wall is translucent, indicating a decrease in thickness and the left ventricular posterior wall is thinner

dilated cardiomyopathy ( J:107823 )

• exhibit global dilation with marked right side atrial and ventricular enlargement, however do not exhibit cardiac hypertrophy

decreased cardiac muscle contractility ( J:107823 )

• 59% decrease in +dP/dt, indicating reduced contractility

decreased heart left ventricle muscle contractility ( J:107823 )

• left ventricle exhibits decreased shortening fraction and velocity of circumferential fiber shortening

abnormal cardiac muscle relaxation ( J:107823 )

• 52% decrease in -dP/dt, indicating that relaxation is prolonged

vision/eye

exophthalmos ( J:107823 )

• exhibit proptosis with unusually dark eyes

respiratory system

respiratory system phenotype ( J:107823 )

N • normal lungs

homeostasis/metabolism

abnormal atrial thrombosis ( J:107823 )

• thrombi are often present within the left atrium

growth/size/body

increased heart weight ( J:107823 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:107823