Analyzing C12orf65 (MTRFR) Expression in Mutant Mouse Models

Document Type

Article

Publication Date

Summer 2022

Keywords

JMG

JAX Location

In: Student Reports, Summer 2022, The Jackson Laboratory

Abstract

Dysfunction of MTRFR is implicated in a number of peripheral neuropathies, including Behr’s Syndrome, Leigh Syndrome and Charcot-Marie Tooth Disease (CMT), which often manifests with optic atrophy, spastic paraplegia, and ataxia among other symptoms. On a cellular level, increased free radical (ROS) production and apoptosis are to be expected when MTRFR is rendered inactive. The Burgess Lab is currently working to produce mice with CRE-inducible human C12orf65 transgenes inserted into the ROSA locus on chromosome 6. These transgenes are either C12orf65 Wild Type (WT) (100% functional MTRFR) or 3K>A Mutant (~60% functional MTRFR) and have been intercrossed with K155,156** knock-in premature truncation of the original C12orf65 gene on Chromosome 5. In mice, the K155,156** mutation is embryonically lethal, though similar mutations are not considered to be terminal in human patients. Expression of the transgenes in tandem with expression of the premature truncation should result in full or partial rescue of function, respectively. We have so far been attempting to confirm the absence of MTRFR in premature truncation models (K155,156**) without the ROSA locus human transgene and the presence of MTRFR in transgenic expression models over homozygotic premature truncation. Confirmation is being done via analysis of mouse embryonic tissues. The transgenic models have been able to survive with no apparent phenotype when compared to their wild type littermates. These mice may serve as an in-vivo model for gene therapy.

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