title: Piebald mutation on a C57BL/6J background.
abstract: The classic piebald mutation in the endothelin receptor type B (Ednrb) gene was found on rolling Nagoya genetic background (PROD-s/s) mice with white coat spotting. To examine whether genetic background influenced the phenotype in the piebald mutant mice, we generated a congenic strain (B6.PROD-s/s), produced by repeated backcrosses to the C57BL/6J (B6) strain. Although B6.PROD-s/s mice showed white coat spotting, 7% of B6.PROD-s/s mice died between 2 and 5 weeks after birth due to megacolon. The PROD-s/s, s/s and Japanese fancy mouse 1 (JF1) strains, which also have piebald mutations on different genetic backgrounds with B6, showed only pigmentation defects without megacolon. In expression analyses, rectums of B6.PROD-s/s with megacolon mice showed ~5% of the level of Ednrb gene expression versus B6 mice. In histological analyses, aganglionosis was detected in the rectum of megacolon animals. The aganglionic rectum was thought to lead to severe constipation and intestinal blockage, resulting in megacolon. We also observed an abnormal intestinal flora, including a marked increase in Bacteroidaceae and Erysipelotrichaceae and a marked decrease in Lactobacillus and Clostridiales, likely inducing endotoxin production and a failure of the mucosal barrier system, leading ultimately to death. These results indicate that the genetic background plays a key role in the development of enteric ganglion neurons, controlled by the Ednrb gene, and that B6 has modifier gene (s) regarding aganglionosis.
authors.affiliation: Research Resources Center, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Fukushima
authors.forename: Kimie
authors.initials: K
authors.lastname: Niimi
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005838:Genotype; D008297:Male; D008531:Megacolon / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D016116:Piebaldism / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism*
chemical_list: C000602969:EDNRB protein, mouse; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D004247:DNA