Abnormalities in cellular adhesion of neuroblastoma and fibroblast models of Lesch Nyhan syndrome.
Lesch Nyhan syndrome is a neurological paediatric condition characterized by mental retardation, choreathotosis and self-mutilation. Biochemically, this condition has been attributed to a deficiency in the purine enzyme, hypoxanthine guanine phosphoribosyltransferase, however, the way this affects the development of the nervous system is still unknown. Ma et al.(15) and Stacey et al.(25) found that hypoxanthine guanine phosphoribosyltransferase-deficient neuroblastoma, differentiated significantly more than cells with this enzyme. Here, we report that adhesion of hypoxanthine guanine phosphoribosyltransferase-deficient neuroblastoma as well as fibroblasts from patients with Lesch Nyhan syndrome, exhibited dramatically enhanced adhesion compared to control cells. This increase in adhesion was dependent upon the cell type, density of the cells and upon the substrate used. Development of the nervous system is dependent on adhesion, in particular in the processes of migration, nucleation, differentiation and fasciculation. Our results suggest that the increased adhesion of hypoxanthine guanine phosphoribosyltransferase-deficient neuroblastoma and fibroblasts in vitro underpins the neuropathology of Lesch Nyhan syndrome.
Stacey
N C
NC
Purine NeuroScience Laboratory, Guy's, King's & St Thomas' Medical School, 5th Floor Guy's Tower, London Bridge, London, SE1 9RT, UK.
Ma
M H
MH
Duley
J A
JA
Connolly
G P
GP
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency; D007926:Lesch-Nyhan Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009447:Neuroblastoma; D014407:Tumor Cells, Cultured
D007041:Hypoxanthine Phosphoribosyltransferase