[Biochemical mechanisms of the development of hereditary galactosemia in W/SSM strain rats].
The W/SSM rat strain with symptoms of inherited galactosemia (cataracts, hepatosplenomegaly, aminoaciduria etc.) was previously developed by selection and inbreeding of Wistar rats highly susceptible to the galactosemic effect of galactose. The decreased activity of galactose-1-phosphate uridyl transferase (Gal-1-PUT) in liver and erythrocytes is the salient biochemical feature of the strain. The crossing experiments have shown that the decrease in Gal-1-PUT activity is not a prerequisite for the expression of main galactosemia symptoms. The experiments excluded the low galactokinase activity and high susceptibility of glucoso-6-phosphate dehydrogenase and phosphoglucomutase to galactose-1-phosphate as probable causes of galactosemia. It was shown that the increased transport of 14C-galactose to erythrocytes is characteristic of the galactosemic rat strain. The intracellular accumulation of galactose concerned with its increased transport was assumed to be a major reason of the development of galactosemia symptoms in W/SSM rats. Genetic analysis has shown that lens lesions in galactosemic rats are controlled by one dominant gene. It is suggested that this gene is responsible for the enhanced transport of galactose into the rat cells and its accumulation in toxic concentrations. The main galactosemic symptoms, including cataracts, result obviously from the pleiotropic effect of this gene, while the decreased activity of Gal-1-PUT may be a consequence of its epistatic effect.
D000818:Animals; D004912:Erythrocytes / Q000201:enzymology; D005686:Galactokinase / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D005693:Galactosemias / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D006824:Hybridization, Genetic; D008099:Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000378:metabolism
D005686:Galactokinase; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase; D005690:Galactose
Issledovanie biokhimicheskikh mekhanizmov razvitiia nasledstvennoĭ galaktozemii u krys linii W/SSM.