REGULATED EXPRESSION OF MATURE HUMAN INSULIN IN THE LIVER OF TRANSGENIC MICE

Transgenic mice expressing either human proinsulin cDNA or mutated pro insulin cDNA in the liver were created. The human proinsulin cDNA was mutated to generate a protein cleavable by the ubiquitous prohormone c onvertase furin, thus leading to mature insulin peptide, All transgeni c lines expressed human C-peptide in the blood, whose level varied acc ording to nutritional conditions, High performance liquid chromatograp hy fractionation of mouse serum revealed that mutant proinsulin was ef fectively processed into mature insulin in vivo. This transgenic mouse model provides a useful tool for further prospects of gene therapy of insulin-dependent diabetes mellitus. (C) 1998 Federation of European Biochemical Societies.