Tyr is the mouse gene that encodes tyrosinase, an enzyme that triggers the first and rate-limiting step in the biosynthesis of melanin. Mutations in Tyr might result in non-functional Tyr protein and, consequently, loss of pigment production. This is a rare genetic condition, known as albinism, described for most animal species and one of the most obvious and simple phenotypes to investigate in model organisms. Mutations in the orthologous human TYR gene are associated with oculocutaneous albinism type 1 (OCA1). Over the last thirty years, the mouse Tyr locus has been studied as a paradigm for how genes and expression domains are organized and regulated in mammalian genomes. This review summarizes the major findings and experimental strategies used, from the production of conventional transgenic mice to the latest CRISPR-Cas9 genome-edited animals. The main conclusion inferred from all of these studies, which extends beyond the analysis of the mouse Tyr locus, is the relevance of analyzing non-coding regulatory DNA elements in their natural chromosomal environment, and not only as randomly inserted transgenes. Further, the identification of evolutionary conserved regulatory sequences might highlight new vulnerable sites in the human TYR gene, whose mutations could also be associated with albinism.
Keywords: albinism; chromatin; insulator; melanin; non-coding genome; retina; tissue-specific expression.
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.