Phenotypes Associated with This Genotype

Genotype
MGI:5883288

• Allelic Composition: Neb^tm2Hgra/Neb^tm2Hgra; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S6/SvEvTac * FVB

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

mortality/aging

premature death ( J:225840 )

• about half of mice die within 3 months of birth, with a median survival of 83 days

• most of the remaining mice survive into adulthood

muscle

decreased quadriceps weight ( J:225840 )

• quadriceps muscle weights are 60-70% smaller than in controls

abnormal muscle fiber morphology ( J:225840 )

• local areas with nemaline rods are seen; in both soleus and EDL muscle, rod bodies make up about 3% of the fiber area

abnormal sarcomere morphology ( J:225840 )

• H-zones are absent and A-band density gradually decreases toward the M-band, indicating thin filaments of variable length

• soleus and EDL muscle show a reduction in thin filament length

abnormal A band morphology ( J:225840 )

• A-band density gradually decreases toward the M-band

abnormal H zone morphology ( J:225840 )

• H-zones are absent

abnormal Z line morphology ( J:225840 )

• Z-disks of sarcomeres are often irregular and wavy

abnormal skeletal muscle fiber size ( J:225840 )

• in the soleus muscle, all three fiber types are smaller

• in the EDL, type IIB fibers are smaller

• the quadriceps muscle shows a severe reduction in type IIB fiber size

• in the EDL muscle, type I and IIA fibers are larger

increased skeletal muscle fiber number ( J:225840 )

• in the soleus muscle, the total number of fibers is increased

decreased skeletal muscle weight ( J:225840 )

• gastrocnemius muscle weights are 60-70% smaller than in controls

• tibialis cranialis and extensor digitorum longus (EDL) weights are much smaller at 5 weeks but less at 6 months

• the soleus muscle weight is increased by about 50% at 6 months

abnormal skeletal muscle fiber type ratio ( J:225840 )

• muscles show a consistent fiber-type switch away from type IIB fibers to oxidative types with hypertrophy of type I and IIA fiber types and severe atrophy of remaining type IIB fibers

• soleus muscle is nearly all type I fibers

• the EDL muscle shows an increased proportion of type I and IIA fibers and a much reduced number of type IIB

• the quadriceps muscle shows a severe reduction in type IIB fiber number

impaired skeletal muscle contractility ( J:225840 )

• reduced force-generating capacity of skeletal muscle, with tetanic force levels reduced 80-90% in EDL muscle

• the maximal specific force at optimal sarcomere length is reduced in both soleus and EDL muscle

behavior/neurological

impaired exercise endurance ( J:225840 )

• mice exercise with reduced duration, speed and distance ran

growth/size/body

decreased body weight ( J:225840 )

• about 40% lower body weight

homeostasis/metabolism

impaired exercise endurance ( J:225840 )

• mice exercise with reduced duration, speed and distance ran

limbs/digits/tail

decreased quadriceps weight ( J:225840 )

• quadriceps muscle weights are 60-70% smaller than in controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nemaline myopathy 2		DOID:0110928	OMIM:256030	J:225840