GENERATION AND CHARACTERIZATION OF TRANSGENIC MICE EXPRESSING A HUMANMUTANT ALPHA-GALACTOSIDASE WITH AN R301Q SUBSTITUTION CAUSING A VARIANT FORM OF FABRY DISEASE

Transgenic mice expressing a human mutant alpha-galactosidase with an R301Q substitution, which was found in a patient with a variant form o f Fabry disease, were established. The mice transcribed a sufficient a mount of alpha-galactosidase mRNA, but the steady-state levels of the enzyme protein were decreased in liver, kidney and heart, only residua l activity being detected in these tissues. The mice will be useful fo r the clarification of the defective regulation of the structurally al tered enzyme protein expressed by the mutant gene at the organ or indi vidual level as well as for the evaluation of drugs that stabilize and /or activate the mutant alpha-galactosidase. (C) 1997 Federation of Eu ropean Biochemical Societies.