title: Fukutin expression in mouse non-muscle somatic organs: its relationship to the hypoglycosylation of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy.
abstract: Recent studies suggest that hypoglycosylation of alpha-dystroglycan (alpha-DG) may play an essential role in the pathogenesis of Fukuyama-type congenital muscular dystrophy (FCMD), which is caused by defects in the fukutin gene and characterized by dystrophic changes in the skeletal muscles and dysplastic lesions in the central nervous system. alpha-DG is expressed in many organs in addition to muscle and brain, although these organs are not affected in FCMD. To elucidate whether or not fukutin protein is involved in the glycosylation of alpha-DG in non-muscle somatic organs, we examined the distribution pattern of fukutin in developing and adult mouse tissues. The fukutin antisera labeled the acinar cells of the pancreas, the renal glomerular and tubular cells, and the epithelium of the bronchi, salivary gland, alimentary tract and skin in both fetal and adult mice. This distribution pattern was also confirmed by in situ hybridization. Antisera against alpha-DG and beta-DG labeled the same cellular populations in each organ, especially along the cell surface membrane. We also examined the glycosylation status of alpha-DG in autopsied FCMD cases (n = 5) and found evidence of hypoglycosylation in the kidney, lung, skin and intestine. These results suggest that fukutin protein is involved in the glycosylation process of alpha-DG in non-muscle somatic organs both during development and in the adult. It is unclear why muscle and brain symptoms predominate in FCMD, however re-evaluation of the functions of alpha-DG and fukutin protein in non-muscle somatic organs may provide valuable insight.
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan. saitoyo@fb3.so-net.ne.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Saito
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Eiko
authors.initials: E
authors.lastname: Ohtsuka-Tsurumi
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itoh
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Makio
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
authors.forename: Makiko
authors.initials: M
authors.lastname: Osawa
mesh_terms: D000293:Adolescent; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004064:Digestive System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D049030:Dystroglycans / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology*; D009928:Organ Specificity; D038081:Organogenesis / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D014166:Transferases; D014781:Viscera / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*
chemical_list: C113587:FKTN protein, human; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D049030:Dystroglycans; C491879:Fcmd protein, mouse; D014166:Transferases