| First Author | Sela I | Year | 2013 |
| Journal | Neuromolecular Med | Volume | 15 |
| Issue | 1 | Pages | 180-91 |
| PubMed ID | 23238814 | Mgi Jnum | J:291580 |
| Mgi Id | MGI:6447943 | Doi | 10.1007/s12017-012-8209-7 |
| Citation | Sela I, et al. (2013) Variable phenotypes of knockin mice carrying the M712T Gne mutation. Neuromolecular Med 15(1):180-91 |
| abstractText | GNE myopathy is a recessive adult onset, slowly progressive distal and proximal myopathy, caused by mutations in the GNE gene. The most frequent mutation in GNE myopathy patients is the Middle Eastern founder mutation M712T. We have generated Gne (M712T/M712T) knockin mice. A high mortality rate in the first generation due to renal failure was recorded (as previously described). However, the following Gne (M712T/M712T) offspring generations could be classified into 3 phenotypic categories: severe, mild and without apparent phenotype. By further crossing between mice with no apparent phenotype, we were able to establish a colony of Gne (M712T/M712T) knockin mice with a high- and long-term survival rate, lacking any renal phenotype. These mice did not present any muscle phenotype (clinical or pathological) for up to 18 months. No correlation was found between the expression of any of the two mRNA Gne isoforms in muscle and the mouse genotype or phenotype. However, the expression of isoform 2 mRNA was significantly higher in the kidney of Gne (M712T/M712T) kidney affected mice compared with control. In contrast, the expression of UPR markers Bip, Chop and of the spliced form of XBP1, was upregulated in muscle of Gne (M712T/M712T) mice compared with controls, but was unchanged in the affected kidney. Thus, Gne defects can affect both muscle and kidney in mouse, but probably through different mechanisms. |
