| First Author | Truch K | Year | 2018 |
| Journal | Hum Mol Genet | Volume | 27 |
| Issue | 6 | Pages | 1078-1092 |
| PubMed ID | 29361054 | Mgi Jnum | J:260791 |
| Mgi Id | MGI:6150563 | Doi | 10.1093/hmg/ddy029 |
| Citation | Truch K, et al. (2018) Analysis of the human SOX10 mutation Q377X in mice and its implications for genotype-phenotype correlation in SOX10-related human disease. Hum Mol Genet 27(6):1078-1092 |
| abstractText | Human SOX10 mutations lead to various diseases including Waardenburg syndrome, Hirschsprung disease, peripheral demyelinating neuropathy, central leukodystrophy, Kallmann syndrome and various combinations thereof. It has been postulated that PCWH as a combination of Waardenburg and Hirschsprung disease, peripheral neuropathy and central leukodystrophy is caused by heterozygous SOX10 mutations that result in the presence of a dominantly acting mutant SOX10 protein in the patient. One such protein with postulated dominant action is SOX10 Q377X. In this study, we generated a mouse model, in which the corresponding mutation was introduced into the Sox10 locus in such a way that Sox10 Q377X is constitutively expressed. Heterozygous mice carrying this mutation exhibited pigmentation and enteric nervous system defects similar to mice in which one Sox10 allele was deleted. However, despite presence of the mutant protein in Schwann cells and oligodendrocytes throughout development and in the adult, we found no phenotypic evidence for neurological defects in peripheral or central nervous systems. In the nervous system, the mutant Sox10 protein did not act in a dominant fashion but rather behaved like a hypomorph with very limited residual function. Our results question a strict genotype-phenotype correlation for SOX10 mutations and argue for the influence of additional factors including genetic background. |
