Fukutin expression in mouse non-muscle somatic organs: its relationship to the hypoglycosylation of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy.
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.
Saito
Yoshiaki
Y
Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan. saitoyo@fb3.so-net.ne.jp
Yamamoto
Tomoko
T
Ohtsuka-Tsurumi
Eiko
E
Oka
Akira
A
Mizuguchi
Masashi
M
Itoh
Masayuki
M
Voit
Thomas
T
Kato
Yoichiro
Y
Kobayashi
Makio
M
Saito
Kayoko
K
Osawa
Makiko
M
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*
C113587:FKTN protein, human; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D049030:Dystroglycans; C491879:Fcmd protein, mouse; D014166:Transferases