Phenotypes associated with this allele

• Allele Symbol: Mbnl1^tm1Sws
• Allele Name: targeted mutation 1, Maurice W Swanson
• Allele ID: MGI:3052922
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mbnl1^tm1Sws/Mbnl1^tm1Sws	involves: 129S1/Sv * C57BL/6J	MGI:3052930
cn2	Mbnl1^tm1Sws/Mbnl1^tm1Sws Mbnl2^tm1Sws/Mbnl2^tm1Sws Tg(Myog-cre)1Eno/0	involves: 129S1/Sv * 129S1/SvImJ * C57BL	MGI:5616749
cx3	Mbnl1^tm1Sws/Mbnl1^tm1Sws Mbnl2^tm1.1Sws/Mbnl2^+	involves: 129S1/Sv * 129S1/SvImJ * C57BL	MGI:5616747
cx4	Mbnl1^tm1Sws/Mbnl1^tm1Sws Mbnl2^tm1.1Sws/Mbnl2^tm1.1Sws	involves: 129S1/Sv * 129S1/SvImJ * C57BL	MGI:5616746
cx5	Mbnl1^tm1Sws/Mbnl1^+ Mbnl2^tm1.1Sws/Mbnl2^tm1.1Sws	involves: 129S1/Sv * 129S1/SvImJ * C57BL	MGI:5616748

Genotype
MGI:3052930

hm1

• Allelic Composition: Mbnl1^tm1Sws/Mbnl1^tm1Sws
• Genetic Background: involves: 129S1/Sv * C57BL/6J

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

muscle

abnormal skeletal muscle fiber morphology ( J:86903 )

• splitting of myofibers

• no major degeneration was detected up to 11 weeks of age

centrally nucleated skeletal muscle fibers ( J:86903 )

• increased nuclei number and central position within myofiber

abnormal muscle physiology ( J:86903 )

• myotonia noted in homozygotes beginning at 6 weeks of age

• delayed muscle relaxation was noticeable after a rest

• electromyographic recordings confirmed myotonic discharges

vision/eye

cataract ( J:86903 )

• mature cataracts seen at 8 months; progressive with age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myotonic disease		DOID:450		J:86903

Genotype
MGI:5616749

cn2

• Allelic Composition: Mbnl1^tm1Sws/Mbnl1^tm1Sws; Mbnl2^tm1Sws/Mbnl2^tm1Sws; Tg(Myog-cre)1Eno/0
• Genetic Background: involves: 129S1/Sv * 129S1/SvImJ * C57BL

growth/size/body

decreased birth body size ( J:218011 )

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:218011 )

• develop severe motor deficits beginning at 12 weeks of age

decreased grip strength ( J:218011 )

skeleton

kyphosis ( J:218011 )

• develop kyphosis beginning at 12 weeks of age

muscle

decreased skeletal muscle fiber size ( J:218011 )

increased variability of skeletal muscle fiber size ( J:218011 )

centrally nucleated skeletal muscle fibers ( J:218011 )

skeletal muscle degeneration ( J:218011 )

• profound deficiency of adult skeletal muscle, with severe muscle pathology including small myofibers, fiber size heterogeneity, and centralized nuclei in nearly all myofibers

Genotype
MGI:5616747

cx3

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

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

Genotype
MGI:5616746

cx4

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

mortality/aging

prenatal lethality, complete penetrance ( J:218011 )

• time of lethality not specified

Genotype
MGI:5616748

cx5

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

mortality/aging

prenatal lethality, incomplete penetrance ( J:218011 )

• reduction in embryonic viability