Tags

Type your tag names separated by a space and hit enter

Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model.
Nat Genet. 1998 Jan; 18(1):60-4.NGen

Abstract

Hirschsprung disease (HSCR, MIM #142623) is a multigenic neurocristopathy (neural crest disorder) characterized by absence of enteric ganglia in a variable portion of the distal colon. Subsets of HSCR individuals also present with neural crest-derived melanocyte deficiencies (Hirschsprung-Waardenburg, HSCR-WS, MIM #277580). Murine models have been instrumental in the identification and analysis of HSCR disease genes. These include mice with deficiencies of endothelin B receptor (Ednrb(s-l); refs 1,2) endothelin 3 (Edn3(ls): refs 1,3) the tyrosine kinase receptor cRet and glial-derived neurotrophic factor. Another mouse model of HSCR disease, Dom, arose spontaneously at the Jackson Laboratory. While Dom/+ heterozygous mice display regional deficiencies of neural crest-derived enteric ganglia in the distal colon, Dom/Dom homozygous animals are embryonic lethal. We have determined that premature termination of Sox10, a member of the SRY-like HMG box family of transcription factors, is responsible for absence of the neural crest derivatives in Dom mice. We demonstrate expression of Sox10 in normal neural crest cells, disrupted expression of both Sox10 and the HSCR disease gene Ednrb in Dom mutant embryos, and loss of neural crest derivatives due to apoptosis. Our studies suggest that Sox10 is essential for proper peripheral nervous system development. We propose SOX10 as a candidate disease gene for individuals with HSCR whose disease does not have an identified genetic origin.

Authors+Show Affiliations

Mouse Embryology Section, Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-4472, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9425902

Citation

Southard-Smith, E M., et al. "Sox10 Mutation Disrupts Neural Crest Development in Dom Hirschsprung Mouse Model." Nature Genetics, vol. 18, no. 1, 1998, pp. 60-4.
Southard-Smith EM, Kos L, Pavan WJ. Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nat Genet. 1998;18(1):60-4.
Southard-Smith, E. M., Kos, L., & Pavan, W. J. (1998). Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nature Genetics, 18(1), 60-4.
Southard-Smith EM, Kos L, Pavan WJ. Sox10 Mutation Disrupts Neural Crest Development in Dom Hirschsprung Mouse Model. Nat Genet. 1998;18(1):60-4. PubMed PMID: 9425902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. AU - Southard-Smith,E M, AU - Kos,L, AU - Pavan,W J, PY - 1998/1/13/pubmed PY - 1998/1/13/medline PY - 1998/1/13/entrez SP - 60 EP - 4 JF - Nature genetics JO - Nat Genet VL - 18 IS - 1 N2 - Hirschsprung disease (HSCR, MIM #142623) is a multigenic neurocristopathy (neural crest disorder) characterized by absence of enteric ganglia in a variable portion of the distal colon. Subsets of HSCR individuals also present with neural crest-derived melanocyte deficiencies (Hirschsprung-Waardenburg, HSCR-WS, MIM #277580). Murine models have been instrumental in the identification and analysis of HSCR disease genes. These include mice with deficiencies of endothelin B receptor (Ednrb(s-l); refs 1,2) endothelin 3 (Edn3(ls): refs 1,3) the tyrosine kinase receptor cRet and glial-derived neurotrophic factor. Another mouse model of HSCR disease, Dom, arose spontaneously at the Jackson Laboratory. While Dom/+ heterozygous mice display regional deficiencies of neural crest-derived enteric ganglia in the distal colon, Dom/Dom homozygous animals are embryonic lethal. We have determined that premature termination of Sox10, a member of the SRY-like HMG box family of transcription factors, is responsible for absence of the neural crest derivatives in Dom mice. We demonstrate expression of Sox10 in normal neural crest cells, disrupted expression of both Sox10 and the HSCR disease gene Ednrb in Dom mutant embryos, and loss of neural crest derivatives due to apoptosis. Our studies suggest that Sox10 is essential for proper peripheral nervous system development. We propose SOX10 as a candidate disease gene for individuals with HSCR whose disease does not have an identified genetic origin. SN - 1061-4036 UR - https://www.unboundmedicine.com/medline/citation/9425902/Sox10_mutation_disrupts_neural_crest_development_in_Dom_Hirschsprung_mouse_model_ L2 - https://doi.org/10.1038/ng0198-60 DB - PRIME DP - Unbound Medicine ER -