Phenotypes Associated with This Genotype

Genotype
MGI:3581453

• Allelic Composition: Lama2^dy-7J/Lama2^dy-7J
• Genetic Background: C57BL/6J-Lama2^dy-7J/J

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

mortality/aging

mortality/aging ( J:134367 )

N • unlike other Lama2 mutants, mice exhibit a normal lifespan

muscle

increased variability of skeletal muscle fiber size ( J:134367 )

• axial, limb, fast-fiber-composed and slow fiber-composed muscles contain myofibers of different calibers separated by monocyte-rich endomysial connective tissue unlike in wild-type mice

skeletal muscle endomysial fibrosis ( J:134367 )

• at 8 weeks of age, mice exhibit signs of muscular dystrophy including widespread endomysial fibrosis

dystrophic muscle ( J:134367 )

• at 8 weeks of age, mice exhibit signs of muscular dystrophy including widespread endomysial fibrosis, focal necrosis and central nuclei typical in regenerated fibers

enhanced skeletal muscle regeneration ( J:134367 )

• at 7 to 8 weeks of age, myofibers contain many centrally located nuclei indicating regeneration of fibers

• mice retain a higher regenerative capacity than Lama2^dy homozygotes but exhibit an increase in centrally located nuclei compared to controls

muscle spasm ( J:82238 )

• beginning at about 2-6 weeks of age, mutant mice exhibit spasms of the hindlimbs that extend the limbs backward or contract them close to the body

myopathy ( J:82238 , J:134367 )

• pathological examination of a 110 day old mutant mouse revealed signs of myopathy (J:82238)

• 4 of 21 mice exhibit progressive skeletal muscle wasting at juvenile ages and bilateral contracture of the hindlimbs by 12 weeks of age (J:134367)

• muscle pathology is similar to in Lama2^dy-2J homozygotes but less severe than in Lama2^dy homozygotes (J:134367)

behavior/neurological

limb grasping ( J:82238 )

• upon being picked up by the tail, beginning around 2-6 weeks of age, a mutant mouse either extends its rear legs backward or contracts them close to the body

hindlimb paresis ( J:134367 )

• by 6 weeks of age, mice exhibit partial paralysis of hindlimbs with some hindlimb function retained at 8 to 10 months of age

• paralysis of hindlimbs is less severe than in Lama2^dy-2J homozygotes

nervous system

abnormal myelination ( J:134367 )

• peripheral nerve roots in the spine exhibit severe hypomyelination

• immature Shwann cells adher lossely to axons and do not extend processes into bundles unlike in wild-type mice

• mice exhibit a consistent defect in myelination compared to Lama2^dy-2J homozygotes that exhibit a variable hypo-myelination phenotype

• most axons roots lack ensheathing processes of Schwann cells

demyelination ( J:82238 )

• pathological examination of a 110 day old mutant mouse identified unmyelinated peripheral nerve fibers

growth/size/body

decreased body weight ( J:134367 )

• after 5 weeks of age

cellular

abnormal basal lamina morphology ( J:134367 )

• contrary to in other Lama2 mutants, the basal lamina is thicker than in wild-type mice

• the basal lamina was absent from non- and pre-myelinating Schwann cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital merosin-deficient muscular dystrophy 1A		DOID:0110636	OMIM:607855	J:134367