Phenotypes Associated with This Genotype

Genotype
MGI:3054527

• Allelic Composition: Tg(DM15)26Bew/0
• Genetic Background: involves: FVB

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

mortality/aging

pregnancy-related premature death ( J:33711 )

♀ • occasional lethality is seen in pregnant female mutants

♀ • this phenotype became less evident in later generations (F3 and later) when male carriers were used

neonatal lethality, complete penetrance ( J:33711 )

• significant neonatal lethality was seen and no homozygous pups were ever produced

behavior/neurological

decreased food intake ( J:33711 , J:93614 )

• older mutants (11-15 months of age) perform at a significantly reduced level under stress testing, with tolerated workload 3-fold lower than in controls (J:93614)

♀ • females display reduced food intake during and after pregnancy (J:33711)

♀ • this phenotype became less evident in later generations (F3 and later) when male carriers were used (J:33711)

abnormal motor coordination/balance ( J:93614 )

• older mice exhibit sporadic yet dramatic transient episodes of walking difficulties

hunched posture ( J:33711 )

♀ • females develop a hunched posture during and after pregnancy

♀ • this phenotype became less evident in later generations (F3 and later) when male carriers were used

cardiovascular system

abnormal myocardial fiber morphology ( J:33711 , J:93614 )

• local whorling interrupts the regular pattern of the myocardium (J:33711)

• increased collagen is seen in the interstitium (J:33711)

• older mice display myocyte disarray, with subcellular degenerative changes, including deformity, multiple vaculolization and mitochondria with abnormal cristae (J:93614)

heart left ventricle hypertrophy ( J:93614 )

• seen in old mutants; left ventricular mass is doubled

thick interventricular septum ( J:93614 )

• interventricular spetal thickness is increased in older mutants

thick ventricular wall ( J:93614 )

• posterior wall is thicker in older mutants

cardiac interstitial fibrosis ( J:93614 )

• seen in older mutants

irregular heartbeat ( J:93614 )

• older mutants exhibit ventricular tachyarrhythmias

abnormal impulse conducting system conduction ( J:93614 )

• junctional rhythm occurs with significant greater frequency in older mutants under light sedation

abnormal P wave ( J:93614 )

• P wave occurs with significantly greater frequency in older mutants under light sedation

hypotension ( J:93614 )

• older mice display depressed systemic systolic and diastolic arterial pressure

cardiomyopathy ( J:33711 , J:93614 )

• obvious cardiomyopathy is seen at 7, 9, or 21 weeks of age (J:33711)

• hypertrophic maladaptive cardiomyopathy with dysrhythmia in older mutants, recapitulating typical features of myotonic dystrophy (J:93614)

• hypertrophic cardiomyopathy is characterized by overt intracellular calcium overload (J:93614)

muscle

abnormal myocardial fiber morphology ( J:33711 , J:93614 )

• local whorling interrupts the regular pattern of the myocardium (J:33711)

• increased collagen is seen in the interstitium (J:33711)

• older mice display myocyte disarray, with subcellular degenerative changes, including deformity, multiple vaculolization and mitochondria with abnormal cristae (J:93614)

heart left ventricle hypertrophy ( J:93614 )

• seen in old mutants; left ventricular mass is doubled

cardiomyopathy ( J:33711 , J:93614 )

• obvious cardiomyopathy is seen at 7, 9, or 21 weeks of age (J:33711)

• hypertrophic maladaptive cardiomyopathy with dysrhythmia in older mutants, recapitulating typical features of myotonic dystrophy (J:93614)

• hypertrophic cardiomyopathy is characterized by overt intracellular calcium overload (J:93614)

abnormal skeletal muscle fiber morphology ( J:93614 )

• skeletal muscle of older mice demonstrates central nuclei, ringed fibers, ragged and torn fibers, hypotrophy with sarcomeric disorganization and sarcoplasmic masses, and accumulation of mitochondria

increased variability of skeletal muscle fiber size ( J:93614 )

• skeletal muscle of older mice exhibits a broad spectrum of fiber sizes

centrally nucleated skeletal muscle fibers ( J:93614 )

• skeletal muscle of older mice demonstrates central nuclei

dystrophic muscle ( J:93614 )

• myotonic dystrophy in older mutants

abnormal muscle relaxation ( J:93614 )

• older mutants exhibit prolonged myotonic discharges characterized by high frequency repetitive potentials in distal limb muscles mechanically stimulated with needle insertion

myopathy ( J:93614 )

• skeletal muscles of older mutants show myopathy including central nuclei, ringed fibers, ragged and torn fibers, broad spectrum of fiber sizes, hypotrophy with sarcomeric disorganization and sarcoplasmic masses, and accumulation of mitochondria

integument

abnormal hair texture ( J:33711 )

♀ • females display bristling hair during and after pregnancy

♀ • this phenotype became less evident in later generations (F3 and later) when male carriers were used

growth/size/body

heart left ventricle hypertrophy ( J:93614 )

• seen in old mutants; left ventricular mass is doubled

cellular

cardiac interstitial fibrosis ( J:93614 )

• seen in older mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myotonic dystrophy type 1		DOID:11722	OMIM:160900	J:93614