Phenotypes Associated with This Genotype

Genotype
MGI:7279103

• Allelic Composition: Crppa^em2Mbp/Crppa^em2Mbp; Myf5^tm3(cre)Sor/Myf5⁺
• Genetic Background: B6.Cg-Myf5^tm3(cre)Sor Crppa^em2Mbp

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

mortality/aging

premature death ( J:324289 )

• some mice die after 10 weeks of age and most die by 20 weeks of age

growth/size/body

decreased body weight ( J:324289 )

slow postnatal weight gain ( J:324289 )

• body weight increases slower at a young age and stops entirely at 10 weeks

muscle

abnormal skeletal muscle morphology ( J:324289 )

• skeletal muscle shows decreased CDP-ribitol levels

• while most mice show dystrophic muscle, a small number of mice show a milder muscle phenotype

increased variability of skeletal muscle fiber size ( J:324289 )

• 12-week-old mice exhibit fiber size variation

centrally nucleated skeletal muscle fibers ( J:324289 )

skeletal muscle fiber necrosis ( J:324289 )

• necrotic and regenerating fibers in 12-week-old mice

decreased skeletal muscle weight ( J:324289 )

• muscle weight (calf, quadriceps, and triceps) are lower at 12 weeks of age

skeletal muscle fibrosis ( J:324289 )

• 12-week-old mice exhibit muscle fibrosis

dystrophic muscle ( J:324289 )

• 12-week-old mice show signs of muscular dystrophy, such as necrotic and regenerating fibers, central nucleation, and fibrous connective tissue infiltration, which are also seen mildly in 4-week-old mice

• adeno-associated virus vector-mediated gene replacement with human CRPPA results in improvement in body weight, grip strength, serum creatine kinase levels, and amelioration of necrotic fibers, fiber size variation, and macrophage and connective tissue infiltration, indicating that the muscular dystrophy pathology is treatable even after onset

• a membrane-permeable CDP-ribitol derivative prodrug, CDP-Rbo(TetA), ameliorates muscular dystrophic changes

• ribitol supplementation has little effect on the dystrophic muscle phenotypes

behavior/neurological

decreased grip strength ( J:324289 )

• grip strength is weaker at 4, 8, and 12 weeks of age

homeostasis/metabolism

increased circulating creatine kinase level ( J:324289 )

• serum creatinine kinase is increased at all ages examined

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2U		DOID:0110295	OMIM:616052	J:324289