Phenotypes Associated with This Genotype

Genotype
MGI:5762541

• Allelic Composition: Des^tm1.1Ccrs/Des⁺
• Genetic Background: involves: 129 * C57BL/6J

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

cardiovascular system

cardiac fibrosis ( J:219616 )

• increased connective tissue in cardiac muscle at 3 months of age, less prominent than in homozygotes

decreased cardiac muscle contractility ( J:219616 )

• decreased myocardial contractility (dP/dtmax value) at 2 years of age, but not earlier

ventricular tachycardia ( J:219616 )

• increased numbers of episodes with ventricular tachycardias (VTs)

• ventricular stimulations lead to a significant increase in the number of VT episodes

irregular heartbeat ( J:219616 )

• arrhythmias

atrial fibrillation ( J:219616 )

• increased numbers of episodes with atrial fibrillation

• long-lasting (>1 min) AF-episodes

ventricular premature beat ( J:219616 )

• significantly increased number of polymorphic premature ventricular contractions (PVCs) during physical stress (10 min swimming exercise)

abnormal impulse conducting system conduction ( J:219616 )

• conduction defects

atrioventricular block ( J:219616 )

• higher grade AV blocks under conditions of stress

• 2nd and 3rd degree AV blocks, never observed in wild-type controls

abnormal heart electrocardiography waveform feature ( J:219616 )

• long-term telemetric baseline electrocardiography recordings revealed atrial and ventricular extrasystoles at 6 months of age

prolonged HV interval ( J:219616 )

• significantly prolonged HV intervals

• however, supra-Hisian AV nodal conductance (AH interval) is normal

abnormal P wave ( J:219616 )

• spontaneous ectopic P-waves at 6 months of age

sinoatrial block ( J:219616 )

• higher grade sino-atrial blocks under conditions of stress

cardiomyopathy ( J:219616 )

• pathological alterations consistent with cardiomyopathy

• 1.9-fold increase in brain natriuretic peptide (BNP) mRNA expression levels at 2 years of age

dilated cardiomyopathy ( J:219616 )

• significant dilated cardiomyopathy in aged mice

muscle

muscle phenotype ( J:219616 )

N • no overt myopathic alterations in skeletal muscle (soleus) tissue at 3- or 16 months of age, despite the presence of desmin-positive protein aggregates

decreased cardiac muscle contractility ( J:219616 )

• decreased myocardial contractility (dP/dtmax value) at 2 years of age, but not earlier

cardiomyopathy ( J:219616 )

• pathological alterations consistent with cardiomyopathy

• 1.9-fold increase in brain natriuretic peptide (BNP) mRNA expression levels at 2 years of age

dilated cardiomyopathy ( J:219616 )

• significant dilated cardiomyopathy in aged mice

abnormal skeletal muscle fiber morphology ( J:219616 )

• step-wise fiber stretching analysis revealed that chemically skinned small fiber bundles isolated from 4.5-mo-old soleus muscles show an increase in biomechanical stiffness, i.e. reduced fiber elasticity, but to a lesser extent than in homozygous mutant fibers

• 2 of 5 fibers display passive-stretch-induced ruptures, unlike wild-type fibers

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myofibrillar myopathy 1		DOID:0080092	OMIM:601419	J:219616