Phenotypes associated with this allele

• Allele Symbol: Csrp3^tm1Crni
• Allele Name: targeted mutation 1, Pico Caroni
• Allele ID: MGI:1858015
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Csrp3^tm1Crni/Csrp3^tm1Crni	Not Specified	MGI:3037157
cx2	Csrp3^tm1Crni/Csrp3^tm1Crni Prkca^tm1Jmk/Prkca^tm1Jmk	involves: 129	MGI:3037158
cx3	Csrp3^tm1Crni/Csrp3^tm1Crni Pln^tm1Egk/Pln^tm1Egk	involves: 129S2/SvPas * CF-1	MGI:3037269
cx4	Csrp3^tm1Crni/Csrp3^tm1Crni Tg(Myh6-ADRBK1)27Wjk/0	involves: C57BL/6 * SJL	MGI:3037429
cx5	Csrp3^tm1Crni/Csrp3^tm1Crni Tg(WTbeta2)4Wjk/0	Not Specified	MGI:3037428

Genotype
MGI:3037157

hm1

• Allelic Composition: Csrp3^tm1Crni/Csrp3^tm1Crni
• Genetic Background: Not Specified

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:38213 )

• 50 to 70% of mice became fatigued between 5 and 10 days of age and died 20 to 30 hours after the onset of symptoms

• mice that did not during the second postnatal week survived to adulthood and displayed a different cardiac phenotype than those that died during the second postnatal

• the penetrance of death during the second postnatal week was higher in offspring from heterozygous crosses than in offspring of either homozygous or heterozygous/homozygous crosses indicating a genetic background effect

cardiovascular system

abnormal intercalated disk morphology ( J:138969 )

• pronounced convolution of the membrane

increased myocardial fiber size ( J:138969 )

• myofibrils are somewhat disorganized

enlarged heart ( J:38213 )

• increase in total heart size

• enlargement affected all 4 chambers equally and was predominantly observed mice that died during the second week of life

increased heart weight ( J:38213 )

• increase in total heart weight

cardiac hypertrophy ( J:38213 )

• observed in both mice that died during the second week of life and in mice that survived to adulthood

dilated heart left ventricle ( J:38213 , J:66250 , J:88510 )

cardiac interstitial fibrosis ( J:38213 )

• observed in mice that survived to adulthood, but not in those that died during the second week of life

abnormal cardiovascular system physiology ( J:66250 )

• sonomicrometry shows right-shifted pressure-volume loops and depressed systolic contractility

dilated cardiomyopathy ( J:38213 , J:66250 , J:88510 )

• disruption of cardiac myofibrillar organization observed (J:38213)

• disorganization of the actin cytoskeleton and myofibrillar apparatus was detected in newborns, prior to overt myopathy (J:38213)

• histologic and ultrastructural features similar to those observed in human dilated cardiomyopathy (J:38213)

decreased cardiac muscle contractility ( J:66250 , J:88510 )

• fractional shortening is reduced from 47-55% in controls to 26-29% in mutants (J:66250)

• cardiomyocytes show a flattened hysteresis loop, showing a similar elevation of intracellular calcium but the extent of shortening is decreased, indicating reduced contractile responsiveness to intracellular calcium changes (J:66250)

• contractility of ventricle is unresponsive to beta-adrenergic receptor stimulation with dobutamine (J:66250)

decreased heart ventricle muscle contractility ( J:38213 )

abnormal heart echocardiography feature ( J:66250 )

• echocardiography in conscious and anesthetized mice indicates hearts with enlarged internal chamber dimensions (end-diastolic dimension and end-systolic dimension) and reduced fractional shortening

abnormal myocardial fiber physiology ( J:66250 )

• cardiomyocytes produce smaller intracellular calcium transients and reduced contractions for similar calcium currents

• cardiomyocytes exhibit a voltage dependent decrease in shortening and relaxation

• reduction in excitation-contraction coupling gain in cardiomyocytes, indicating that efficacy of activation of calcium sparks by calcium influx through the L-type calcium channel is reduced

congestive heart failure ( J:66250 )

• mice are in functional heart failure

muscle

abnormal intercalated disk morphology ( J:138969 )

• pronounced convolution of the membrane

increased myocardial fiber size ( J:138969 )

• myofibrils are somewhat disorganized

dilated cardiomyopathy ( J:38213 , J:66250 , J:88510 )

• disruption of cardiac myofibrillar organization observed (J:38213)

• disorganization of the actin cytoskeleton and myofibrillar apparatus was detected in newborns, prior to overt myopathy (J:38213)

• histologic and ultrastructural features similar to those observed in human dilated cardiomyopathy (J:38213)

decreased cardiac muscle contractility ( J:66250 , J:88510 )

• fractional shortening is reduced from 47-55% in controls to 26-29% in mutants (J:66250)

• cardiomyocytes show a flattened hysteresis loop, showing a similar elevation of intracellular calcium but the extent of shortening is decreased, indicating reduced contractile responsiveness to intracellular calcium changes (J:66250)

• contractility of ventricle is unresponsive to beta-adrenergic receptor stimulation with dobutamine (J:66250)

decreased heart ventricle muscle contractility ( J:38213 )

cellular

cardiac interstitial fibrosis ( J:38213 )

• observed in mice that survived to adulthood, but not in those that died during the second week of life

abnormal actin cytoskeleton morphology ( J:38213 )

• disorganization of the actin cytoskeleton and myofibrillar apparatus was detected in newborns, prior to overt myopathy

growth/size/body

enlarged heart ( J:38213 )

• increase in total heart size

• enlargement affected all 4 chambers equally and was predominantly observed mice that died during the second week of life

increased heart weight ( J:38213 )

• increase in total heart weight

cardiac hypertrophy ( J:38213 )

• observed in both mice that died during the second week of life and in mice that survived to adulthood

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congestive heart failure		DOID:6000		J:66250
dilated cardiomyopathy 1M		DOID:0110449	OMIM:607482	J:38213

Genotype
MGI:3037158

cx2

• Allelic Composition: Csrp3^tm1Crni/Csrp3^tm1Crni; Prkca^tm1Jmk/Prkca^tm1Jmk
• Genetic Background: involves: 129

cardiovascular system

cardiovascular system phenotype ( J:88510 )

N • partial rescue of the dilated cardiomyopathic phenotype observed in Csrp3^tm1Crni homozygotes

N • normal ventricular performance

dilated heart left ventricle ( J:88510 )

• relative to wild-type

• observed dilation was reduced relative to Csrp3^tm1Crni homozygotes

Genotype
MGI:3037269

cx3

• Allelic Composition: Csrp3^tm1Crni/Csrp3^tm1Crni; Pln^tm1Egk/Pln^tm1Egk
• Genetic Background: involves: 129S2/SvPas * CF-1

cardiovascular system

cardiac hypertrophy ( J:58299 )

• indicated by a slight increase in the heart weight/body weight ratio

• heart structure is otherwise normalized compared to conditions in mice homozygous for with Csrp3^Tm1Crni only

• more normal heart size

• normalized myofibrillar organization

• no fibrosis

• normal cardiac chamber dimensions as indicated by echocardiography

increased cardiac muscle contractility ( J:58299 )

• increased contractile properties similar to those of mice homozygous for Pln^tm1Egk only

• normalized left ventricular relaxation and diastolic function

decreased heart rate ( J:58299 )

• slightly decreased relative to wild-type

muscle

increased cardiac muscle contractility ( J:58299 )

• increased contractile properties similar to those of mice homozygous for Pln^tm1Egk only

• normalized left ventricular relaxation and diastolic function

growth/size/body

cardiac hypertrophy ( J:58299 )

• indicated by a slight increase in the heart weight/body weight ratio

• heart structure is otherwise normalized compared to conditions in mice homozygous for with Csrp3^Tm1Crni only

• more normal heart size

• normalized myofibrillar organization

• no fibrosis

• normal cardiac chamber dimensions as indicated by echocardiography

Genotype
MGI:3037429

cx4

• Allelic Composition: Csrp3^tm1Crni/Csrp3^tm1Crni; Tg(Myh6-ADRBK1)27Wjk/0
• Genetic Background: involves: C57BL/6 * SJL

cardiovascular system

cardiovascular system phenotype ( J:48062 , J:66250 )

N • partial rescue of the dilated cardiomyopathic phenotype observed in Csrp3^tm1Crni homozygotes, with some persistence of decreased contractility and fibrosis (J:48062)

N • no observed ventricular dilation (J:48062)

N • cellular and whole heart function is restored to normal (J:66250)

cardiac interstitial fibrosis ( J:48062 )

decreased heart ventricle muscle contractility ( J:48062 )

• relative to wild-type

• partial rescue of decreased contractility observed in Csrp3^tm1Crni homozygotes

muscle

decreased heart ventricle muscle contractility ( J:48062 )

• relative to wild-type

• partial rescue of decreased contractility observed in Csrp3^tm1Crni homozygotes

cellular

cardiac interstitial fibrosis ( J:48062 )

Genotype
MGI:3037428

cx5

• Allelic Composition: Csrp3^tm1Crni/Csrp3^tm1Crni; Tg(WTbeta2)4Wjk/0
• Genetic Background: Not Specified

cardiovascular system

dilated heart left ventricle ( J:48062 )

dilated cardiomyopathy ( J:48062 )

• the overexpression of ADRB2 did not influence the dilated cardiomyopathy observed in Csrp3^tm1Crni homozygotes

decreased heart ventricle muscle contractility ( J:48062 )

muscle

dilated cardiomyopathy ( J:48062 )

• the overexpression of ADRB2 did not influence the dilated cardiomyopathy observed in Csrp3^tm1Crni homozygotes

decreased heart ventricle muscle contractility ( J:48062 )