Phenotypes Associated with This Genotype

Genotype
MGI:6149568

• Allelic Composition: Ano5^tm1Lrk/Ano5^tm1Lrk
• Genetic Background: involves: C57BL/6

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

muscle

muscle phenotype ( J:235810 )

N • specific force of extensor digitorum longus (EDL) and tibialis anterior (TA) muscle contraction

N • needle electromyography, evoked compound muscle action potential (CMAP) and electrical impedance myography (EIM) readings in hindlimbs

abnormal skeletal muscle morphology ( J:235810 )

• intramuscular deposits in ~25% of fibers: irregularly contoured red areas upon trichrome staining, which are aggregates comprising densely packed accumulations of vesicular or tubular membranes or haphazardly oriented and loosely packed interconnecting tubular formations with fuzzy inner tubules

• sub-sarcolemmal accumulation of mitochondria

• degenerating mitochondria

abnormal skeletal muscle fiber mitochondrial morphology ( J:235810 )

• degenerating mitochondria in skeletal muscle

• sub-sarcolemmal accumulation of mitochondria in skeletal muscle

skeletal muscle fiber necrosis ( J:235810 )

• extensive delay in regeneration after cardiotoxin injection of tibialis anterior (TA) and gastrocnemius (GAS) muscle

abnormal gastrocnemius morphology ( J:235810 )

• significantly reduced average muscle fiber diameter

abnormal tibialis anterior morphology ( J:235810 )

• reduced average muscle fiber diameter

• specific force of contraction

centrally nucleated skeletal muscle fibers ( J:235810 )

abnormal diaphragm morphology ( J:235810 )

• 15% reduction in specific force of diaphragm muscle contraction

delayed skeletal muscle regeneration ( J:235810 )

• extensive delay in regeneration after cardiotoxin injection of tibialis anterior (TA) and gastrocnemius (GAS) muscle

impaired skeletal muscle regeneration ( J:235810 )

• mean fiber diameter of tibialis anterior (TA) and gastrocnemius (GAS) muscle remained significantly reduced 3 months after last cardiotoxin injection

• impaired myoblast progenitor cell fusion in vitro: only 48% of cells fused to form multi-nucleated myotubes (vs 74% wild-type); myotubes shorter, and many with ovoid shape; lower average number of nuclei per myotube

increased muscle fatigability ( J:235810 )

• prone to frequent breaks during 1h/week 2 months treadmill exercise regime

cellular

abnormal skeletal muscle fiber mitochondrial morphology ( J:235810 )

• degenerating mitochondria in skeletal muscle

• sub-sarcolemmal accumulation of mitochondria in skeletal muscle

skeletal muscle fiber necrosis ( J:235810 )

• extensive delay in regeneration after cardiotoxin injection of tibialis anterior (TA) and gastrocnemius (GAS) muscle

abnormal mitochondrial physiology ( J:235810 )

• significantly reduced citrate synthase activity in skeletal muscle

• degenerating mitochondria in skeletal muscle

homeostasis/metabolism

increased circulating creatine kinase level ( J:235810 )

• 2x higher in serum

limbs/digits/tail

abnormal gastrocnemius morphology ( J:235810 )

• significantly reduced average muscle fiber diameter

abnormal tibialis anterior morphology ( J:235810 )

• reduced average muscle fiber diameter

• specific force of contraction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2L		DOID:0110284	OMIM:611307	J:235810