| First Author | Schisler JC | Year | 2016 |
| Journal | Afr J Cell Pathol | Volume | 6 |
| Issue | 4 | Pages | 28-36 |
| PubMed ID | 28593200 | Mgi Jnum | J:245069 |
| Mgi Id | MGI:5915579 | Citation | Schisler JC, et al. (2016) SKELETAL MUSCLE MITOCHONDRIAL ALTERATIONS IN CARBOXYL TERMINUS OF HSC70 INTERACTING PROTEIN (CHIP) -/- MICE. Afr J Cell Pathol 6(4):28-36 |
| abstractText | 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. |
