Phenotypes Associated with This Genotype

Genotype
MGI:5616747

• Allelic Composition: Mbnl1^tm1Sws/Mbnl1^tm1Sws; Mbnl2^tm1.1Sws/Mbnl2⁺
• Genetic Background: involves: 129S1/Sv * 129S1/SvImJ * C57BL

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

mortality/aging

premature death ( J:218011 )

• mice do not survive beyond 23 weeks of age

growth/size/body

enlarged heart ( J:218011 )

• hearts are enlarged and heart/body weight ratios are increased about 60%

heart left ventricle hypertrophy ( J:218011 )

decreased body weight ( J:218011 )

• body weight is maintained at about 30% less than single Mbnl1 homozygotes

behavior/neurological

abnormal motor coordination/balance ( J:218011 )

• 8-10 week old mice develop severe mobility problems

impaired coordination ( J:218011 )

• 8-10 week old mice show impaired rotarod performance

decreased grip strength ( J:218011 )

• muscle weakness is seen as early as 4 weeks of age in the grip strength test

cardiovascular system

dilated heart atrium ( J:218011 )

enlarged heart ( J:218011 )

• hearts are enlarged and heart/body weight ratios are increased about 60%

heart left ventricle hypertrophy ( J:218011 )

cardiac fibrosis ( J:218011 )

• fibrosis is seen in enlarged right atria

cardiac interstitial fibrosis ( J:218011 )

• interstitial myocardial fibrosis

atrioventricular block ( J:218011 )

• PR interval is prolonged, indicating a first degree AV block

prolonged PR interval ( J:218011 )

prolonged QRS complex duration ( J:218011 )

prolonged QT interval ( J:218011 )

muscle

heart left ventricle hypertrophy ( J:218011 )

muscle degeneration ( J:218011 )

• increased muscle fiber size variation, atrophic and splitting fibers, and increased numbers of central nuclei indicative of muscle degeneration/regeneration are seen in muscles at 10-16 weeks of age

impaired muscle relaxation ( J:218011 )

• myotonia is increased compared to single Mbnl1 homozygotes, with both the amplitude and duration of discharges increased 2.5 to about 4-fold

• however, the ejection fraction is not different from wild-type mice

progressive muscle weakness ( J:218011 )

• progressive muscle weakness and wasting

nervous system

abnormal neuromuscular synapse morphology ( J:218011 )

• loss of mature neuromuscular junctions, and an increase in degenerated (fragmented endplates) and premature neuromuscular junctions in tibialis anterior muscles

cellular

cardiac interstitial fibrosis ( J:218011 )

• interstitial myocardial fibrosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myotonic disease		DOID:450		J:218011