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Sdha+/- Rats Display Minimal Muscle Pathology Without Significant Behavioral or Biochemical Abnormalities. J Neuropathol Exp Neurol 2018 08 01;77(8):665-672

Date

06/01/2018

Pubmed ID

29850869

Pubmed Central ID

PMC6044411

DOI

10.1093/jnen/nly042

Scopus ID

2-s2.0-85054028838   3 Citations

Abstract

Mitochondrial diseases (MDs) result from alteration of the mitochondrial respiratory chain (MRC) function. Despite the prevalence of MDs in the population, the paucity of animal models available limits the understanding of these disorders. Mutations in SDHA, a gene that codes for the alpha subunit of succinate dehydrogenase (SDH), can cause some forms of MD. SDHA is a crucial contributor to MRC function. In order to expand the range of MD animal models available, we attempted to generate a Sdha knockout rat. Since homozygous Sdha-/- rats could neither be identified in newborn litters, nor as early as embryonic day 14, we evaluated wild-type (WT) and heterozygous Sdha+/- genotypes. No differences in behavioral, biochemical, or molecular evaluations were observed between WT and Sdha+/- rats at 6 weeks or 6 months of age. However, 30% of Sdha+/- rats displayed mild muscle fiber atrophy with rare fibers negative for cytochrome oxidase and SDH on histochemical staining. Collectively, our data provide additional evidence that modeling SDH mutations in rodents may be challenging due to animal viability, and heterozygous rats are insufficiently symptomatic at a phenotypic and molecular level to be of significant use in the study of SDH deficiency.

Author List

Siebers EM, Choi MJ, Tinklenberg JA, Beatka MJ, Ayres S, Meng H, Helbling DC, Takizawa A, Bennett B, Garces AM, Dias Duarte Machado LG, Dimmock D, Dwinell MR, Geurts AM, Lawlor MW

Authors

Brian Bennett D.Phil. Professor and Chair in the Physics department at Marquette University
Melinda R. Dwinell PhD Professor in the Physiology department at Medical College of Wisconsin
Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Michael W. Lawlor MD, PhD Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
DNA, Mitochondrial
Electron Transport Complex II
Gene Knockout Techniques
Hand Strength
Male
Muscle, Skeletal
Rats
Rats, Transgenic
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0