Phenotypes associated with this allele

• Allele Symbol: Tg(CAG-DMPK*)1323Coop
• Allele Name: transgene insertion 1323, Thomas A Cooper
• Allele ID: MGI:5426792
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	A1cf^Tg(Myh6-cre/Esr1*)1Jmk/A1cf^+ Tg(CAG-DMPK*)1323Coop/0	involves: FVB	MGI:5426794
cn2	Tg(ACTA1-cre/ERT2)97.16Mtz/0 Tg(CAG-DMPK*)1323Coop/0	involves: FVB	MGI:5426828

Genotype
MGI:5426794

cn1

• Allelic Composition: A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺; Tg(CAG-DMPK*)1323Coop/0
• Genetic Background: involves: FVB

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

mortality/aging

premature death ( J:127391 )

• mutants treated with tamoxifen at 8-9 weeks of age to induce Cre-mediated recombination die within 2 weeks of tamoxifen injection

cardiovascular system

abnormal myocardial fiber morphology ( J:127391 )

• cardiomyocyte cytoplasm of tamoxifen treated mutants appears pale in patchy areas and contains variably prominent numbers of pink granules; focally abundant mitochondria correlate with the pink granules

• in some myocytes of tamoxifen treated mutants, aggregates of proliferating membranes of the sarcoplasmic reticulum are seen

• however, sarcomeres and Z-lines appear normal

increased myocardial fiber size ( J:127391 )

• mutants treated with tamoxifen exhibit myocyte hypertrophy with enlarged, irregular myocyte nuclei

decreased heart left ventricle wall thickness ( J:127391 )

• thinning of the left ventricular wall after treatment with tamoxifen

dilated heart left ventricle ( J:127391 )

• dilation of the left ventricle after treatment with tamoxifen

cardiac interstitial fibrosis ( J:127391 )

• rare degenerating myocytes and focal areas of mild interstitial fibrosis are seen in mutants treated with tamoxifen

abnormal cardiovascular system physiology ( J:127391 )

• mutants treated with tamoxifen exhibit cardiac dysfunction in both systolic and diastolic parameters

dilated cardiomyopathy ( J:127391 )

• mutants treated with tamoxifen at 8-9 weeks of age to induce Cre-mediated recombination develop dilated cardiomyopathy

decreased diastolic filling velocity ( J:127391 )

• peak early diastolic filling velocity is decreased by more than 30% in mutants treated with tamoxifen

decreased cardiac muscle contractility ( J:127391 )

• systolic function of mutants treated with tamoxifen exhibits a 50% or greater decrease in peak aortic flow velocity and both mean and peak acceleration

abnormal cardiac muscle relaxation ( J:127391 )

• isovolumic relaxation time is prolonged by more than 50% in mutants treated with tamoxifen

irregular heartbeat ( J:127391 )

• standard deviation of RR intervals is increased 5-fold after tamoxifen administration

atrioventricular block ( J:127391 )

• at 4 days after the last day of tamoxifen administration, mice show 2:1 atrioventricular block

prolonged PR interval ( J:127391 )

• progressive lengthening of the PR interval is seen beginning 2 days after the last day of tamoxifen administration

prolonged QRS complex duration ( J:127391 )

• widening of the QRS complex is seen beginning 2 days after the last day of tamoxifen administration

muscle

abnormal myocardial fiber morphology ( J:127391 )

• cardiomyocyte cytoplasm of tamoxifen treated mutants appears pale in patchy areas and contains variably prominent numbers of pink granules; focally abundant mitochondria correlate with the pink granules

• in some myocytes of tamoxifen treated mutants, aggregates of proliferating membranes of the sarcoplasmic reticulum are seen

• however, sarcomeres and Z-lines appear normal

increased myocardial fiber size ( J:127391 )

• mutants treated with tamoxifen exhibit myocyte hypertrophy with enlarged, irregular myocyte nuclei

dilated cardiomyopathy ( J:127391 )

• mutants treated with tamoxifen at 8-9 weeks of age to induce Cre-mediated recombination develop dilated cardiomyopathy

decreased cardiac muscle contractility ( J:127391 )

• systolic function of mutants treated with tamoxifen exhibits a 50% or greater decrease in peak aortic flow velocity and both mean and peak acceleration

abnormal cardiac muscle relaxation ( J:127391 )

• isovolumic relaxation time is prolonged by more than 50% in mutants treated with tamoxifen

cellular

cardiac interstitial fibrosis ( J:127391 )

• rare degenerating myocytes and focal areas of mild interstitial fibrosis are seen in mutants treated with tamoxifen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myotonic dystrophy type 1		DOID:11722	OMIM:160900	J:127391

Genotype
MGI:5426828

cn2

• Allelic Composition: Tg(ACTA1-cre/ERT2)97.16Mtz/0; Tg(CAG-DMPK*)1323Coop/0
• Genetic Background: involves: FVB

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:132154 )

• on a graded treadmill protocol, mutants treated with tamoxifen show a decrease in the time of drop off from the treadmill compared to controls

abnormal locomotor behavior ( J:132154 )

• by 4 weeks after tamoxifen administration, 70% of mutants show reduced mobility

abnormal gait ( J:132154 )

• by 4 weeks after tamoxifen administration, 70% of mutants show abnormal gait

muscle

abnormal skeletal muscle fiber morphology ( J:132154 )

• mutants treated with tamoxifen exhibit increased numbers of smaller myocytes, scattered basophilic fibers, acute myofibrillar degeneration with significant numbers of necrotic fibers and many fibers with basophilic cytoplasm and central nuclei consistent with regeneration

• four weeks after tamoxifen administration, mutants show a loss in fibers expressing solely slow twitch myosin and an increase in the number of fibers showing simultaneous expression of slow and fast twitch myosin isoforms

decreased skeletal muscle size ( J:132154 )

• by 4 weeks after tamoxifen administration, mutants show a severe reduction in muscle size

• muscle wasting progressively worsens with a 15% reduction in diameter by 4 weeks after tamoxifen administration

skeletal muscle degeneration ( J:132154 )

• mutants treated with tamoxifen exhibit severe and progressive skeletal muscle wasting and degeneration

skeletal muscle fibrosis ( J:132154 )

• mutants treated with tamoxifen exhibit focal regions with increased fibrosis in skeletal muscle

impaired muscle relaxation ( J:132154 )

• mutants treated with tamoxifen to induce cre-recombination exhibit sustained myotonia, with waxing and waning myotonic runs noted on electromyogram

• mutants not treated with tamoxifen also develop myotonia, indicating basal leakiness of the transgene, however they do not show overt skeletal muscle wasting, histological abnormalities or muscle dysfunction as do tamoxifen treated mutants

skeleton

kyphosis ( J:132154 )

• by 4 weeks after tamoxifen administration, 70% of mutants show kyphosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myotonic dystrophy type 1		DOID:11722	OMIM:160900	J:132154