Chracterization of the effect of the Mnm(c) modifying allele on a new, CRISPR-based mouse model of SMARD1


Alex Thele

Document Type


Publication Date

Summer 2017

JAX Location

In: Student Reports, Summer 2017, Jackson Laboratory


Spinal muscular atrophy with respiratory distress, type 1 (SMARD1) is a rare autosomal recessive disease caused by mutation in the Ighmbp2 gene. Mutations in this gene in mice cause a SMARD1-like phenotype and serve as useful animal models of neuromuscular degeneration (nmd) . There is a second-site modifying allele (MnmC ) that rescues the historical SMARD1 mouse model, nmd2J , in a semi-dominant fashion. The purpose of this experiment was to determine if the Mnmc modifying allele suppressed the phenotype of a new, CRISPR-based mutation in the Ighmbp2 gene, C57BLl6J-lghmbp2em3cx (em3). We hypothesized that the modifier would also rescue the phenotype of the em3 mice. To test this hypothesis, data was collected on several litters on em3 mice with and without a transgene containing the modifying allele and on C57BLl6J control s. General information collected included lifespan and animal weights, as well as analysis of the myelinated axon counts in the femoral nerve and neuromuscular junctions of the medical gastrocnemius (MG). Our findings suggest that there is no significant difference between the groups of em3 with the transgene carrying the modifier and those without it. Based on these findings, we conclude that the modifying allele does not rescue the em3 mutant phenotype.

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