Mouse Genome Informatics
cn1
    Tg(CAG-DMPK*)1323Coop/0
Tg(Myh6-cre/Esr1*)1Jmk/0

involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants treated with tamoxifen at 8-9 weeks of age to induce Cre-mediated recombination die within 2 weeks of tamoxifen injection

cardiovascular system
• 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
• mutants treated with tamoxifen exhibit myocyte hypertrophy with enlarged, irregular myocyte nuclei
• dilation of the left ventricle after treatment with tamoxifen
• thinning of the left ventricular wall after treatment with tamoxifen
• rare degenerating myocytes and focal areas of mild interstitial fibrosis are seen in mutants treated with tamoxifen
• mutants treated with tamoxifen exhibit cardiac dysfunction in both systolic and diastolic parameters
• mutants treated with tamoxifen at 8-9 weeks of age to induce Cre-mediated recombination develop dilated cardiomyopathy
• peak early diastolic filling velocity is decreased by more than 30% in mutants treated with tamoxifen
• systolic function of mutants treated with tamoxifen exhibits a 50% or greater decrease in peak aortic flow velocity and both mean and peak acceleration
• isovolumic relaxation time is prolonged by more than 50% in mutants treated with tamoxifen
• standard deviation of RR intervals is increased 5-fold after tamoxifen administration
• at 4 days after the last day of tamoxifen administration, mice show 2:1 atrioventricular block
• progressive lengthening of the PR interval is seen beginning 2 days after the last day of tamoxifen administration
• widening of the QRS complex is seen beginning 2 days after the last day of tamoxifen administration

muscle
• 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
• mutants treated with tamoxifen exhibit myocyte hypertrophy with enlarged, irregular myocyte nuclei
• mutants treated with tamoxifen at 8-9 weeks of age to induce Cre-mediated recombination develop dilated cardiomyopathy
• systolic function of mutants treated with tamoxifen exhibits a 50% or greater decrease in peak aortic flow velocity and both mean and peak acceleration
• isovolumic relaxation time is prolonged by more than 50% in mutants treated with tamoxifen

Mouse Models of Human Disease
OMIM IDRef(s)
Myotonic Dystrophy 1; DM1 160900 J:127391


Mouse Genome Informatics
cn2
    Tg(ACTA1-cre/ERT2)97.16Mtz/0
Tg(CAG-DMPK*)1323Coop/0

involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• on a graded treadmill protocol, mutants treated with tamoxifen show a decrease in the time of drop off from the treadmill compared to controls
• by 4 weeks after tamoxifen administration, 70% of mutants show reduced mobility
• by 4 weeks after tamoxifen administration, 70% of mutants show abnormal gait

muscle
• 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
• 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
• mutants treated with tamoxifen exhibit severe and progressive skeletal muscle wasting and degeneration
• mutants treated with tamoxifen exhibit focal regions with increased fibrosis in skeletal muscle
• 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
• by 4 weeks after tamoxifen administration, 70% of mutants show kyphosis

Mouse Models of Human Disease
OMIM IDRef(s)
Myotonic Dystrophy 1; DM1 160900 J:132154