title: Genetic variation in the GDNF promoter affects its expression and modifies the severity of Hirschsprung's disease (HSCR) in rats carrying Ednrb(sl) mutations.
abstract: Glial cell line-derived neurotrophic factor (GDNF) is necessary for the migration of neural crest stem cells in the gut. However, mutations in GDNF per se are deemed neither necessary nor sufficient to cause Hirschsprung's disease (HSCR). In a previous study, a modifier locus on chromosome 2 in rats carrying Ednrb(sl) mutations was identified, and several mutations in the putative regulatory region of the Gdnf gene in AGH-Ednrb(sl) rats were detected. Specifically, the mutation -232C>T has been shown to be strongly associated with the severity of HSCR. In the present study, the influence of genetic variations on the transcription of the Gdnf gene was tested using dual-luciferase assay. Results showed that the mutation -613C>T, located near the mutation -232C>T in AGH-Ednrb(sl) rats, decreased Gdnf transcription in an in vitro dual-luciferase expression assay. These data suggested an important role of -613C in Gdnf transcription. Expression levels of the Gdnf gene may modify the severity of HSCR in rats carrying Ednrb(sl) mutations.
authors: College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China; College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors: Jieping
authors: J
authors: Huang
authors: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: dangruihua@nwsuaf.edu.cn.
authors: Ruihua
authors: R
authors: Dang
authors: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan; Division of Microbiology and Genetics, Center for Animal Resources and Development, Kumamoto, Japan.
authors: Daisuke
authors: D
authors: Torigoe
authors: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors: Anqi
authors: A
authors: Li
authors: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: leichuzhao1118@126.com.
authors: Chuzhao
authors: C
authors: Lei
authors: Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Aomori, Japan.
authors: Nobuya
authors: N
authors: Sasaki
authors: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
authors: Jinxi
authors: J
authors: Wang
authors: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
authors: Takashi
authors: T
authors: Agui
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D051381:Rats; D011922:Rats, Mutant Strains; D044023:Receptor, Endothelin B / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D044023:Receptor, Endothelin B
keywords: Dual-luciferase assay; Gdnf; Genetic variation; HSCR; Promoter