Genetically engineered mutant strains of mice have become invaluable too to decipher complex biological processes, such as ECM assembly, and to dissect phenotypic overlaps, like the genodermatoses. Homologous gene targe ing in embryonic stem (ES) cells is increasingly favored over the transgen approach because it allows the study of mutations in homozygosity and without altering the remainder of the genome (1). Homologous gene targeting has been successfully employed to abrogate the expression or alter the structure of ECM-coding genes (2,3). In both cases, the experimental protocol consists of the following three steps: a. construction of the targeting vector; b. homologous recombination in ES cells; and c. generation of mutant mouse strains.