African Journal of
Cellular Pathology

OFFICIAL PUBLICATION OF THE SOCIETY FOR CELLULAR PATHOLOGY SCIENTISTS OF NIGERIA
  • Abbreviation: Afr. J. Cell. Path
  • Language: English
  • ISSN: 2449-0776
  • DOI: 10.5897/AJCPath
  • Start Year: 2013
  • Published Articles: 80

SKELETAL MUSCLE MITOCHONDRIAL ALTERATIONS IN CARBOXYL TERMINUS OF HSC70 INTERACTING PROTEIN (CHIP)-/- MICE

Jonathan C. Schisler
  • Jonathan C. Schisler
  • McAllister Heart Institute, University of North Carolina, Chapel Hill, NC USA
  • Google Scholar
Cam Patterson
  • Cam Patterson
  • McAllister Heart Institute, University of North Carolina, Chapel Hill, NC USA
  • Google Scholar
Monte S. Willis
  • Monte S. Willis
  • McAllister Heart Institute, University of North Carolina, Chapel Hill, NC USA
  • Google Scholar


  • Article Number - B5DC83765698
  • Vol.6(4), pp. 28-36 , April 2016
  •  Received: 23 February 2016
  •  Accepted: 20 March 2016
  •  Published: 30 April 2016

Abstract

Aim: Hereditary ataxias are characterized by a slowly progressive loss of gait, hand, speech, and eye coordination and cerebellar atrophy. A subset of these, including hypogonadism, are inherited as autosomal recessive traits involving coding mutations of genes involved in ubiquitination including RNF216, OTUD4, and STUB1. Cerebellar CHIPopathy (MIM 615768) is a form of autosomal recessive spinocerebellar ataxia (SCAR16) and when accompanied with hypogonadism, clinically resembles the Gordon Holmes Syndrome (GHS). A causal missense mutation in the gene that encodes the carboxy terminus of HSP-70 interacting protein (CHIP) protein was reported for the first time in 2014. CHIP-/- mice were found to phenocopy the motor deficiencies and some aspects of the hypogonadism observed in patients with STUB1 mutations. However, mechanisms responsible for these deficits are not known.

Methods: In a survey of skeletal muscle by transmission electron microscopy,

Results: CHIP-/- mice at 6 months of age were found to have morphological changes consistent with increased sarcoplasmic reticulum compartments in quadriceps muscle and gastrocnemius (toxic oligomers and tubular aggregates), but not in soleus.

Conclusion: Since CHIP has been implicated in ER stress in non-muscle cells, these findings illustrate potential parallel roles of CHIP in the muscle sarcoplasmic reticulum, a hypothesis that may be clinically relevant in a variety of common muscular and cardiac diseases.

Key words: STUB1, muscle, ER stress