Mouse coat color mutations: From fancy mice to functional genomics

Abstract

Mouse coat color mutations have a long history in biomedical research. The viable and visible phenotype of most coat color mutations has made the pigment cell, the melanocyte, an ideal system for genetic, molecular, and cellular analysis. Molecular cloning and analysis of many of the different coat color mutations have revealed the roles of a diverse range of genes, and today we know more about the pathways and proteins that regulate the development and function of pigment cells than we know about most other cell types in mammalian organisms. Coat color mutations have also provided novel insights into stem cell biology and human diseases, including melanoma. In the future, it will be important to build on this history and knowledge by taking advantage of the extensive repertoire of recently developed genome-wide methodologies, available genomic information, and the powerful methods that have been developed for modifying the mouse genome to systematically dissect the development and function of this important cell type. The usefulness of coat color mutations has just begun to emerge. Developmental Dynamics 235: 2401-2411, 2006.

Differential Gene Expression of TRPM1, the Potential Cause of Congenital Stationary Night Blindness and Coat Spotting Patterns (LP) in the Appaloosa Horse (Equus caballus)

“…Defects in a light-gaited TRP channel results in a loss of phototransduction in Drosophila (reviewed in Kim 2004). Although the specific function of TRPM1 has yet to be described, cellular sensation and intercellular signaling are vital for normal melanocyte migration (reviewed in Steingrímsson et al 2006). In mice and humans, the promoter region of this gene contains four consensus binding sites for a melanocyte transcription factor, MITF Zhiqi et al 2004).…”

Digital gene expression for non-model organisms

“…Studies of additional cheetah samples will a Expression levels are given as tags per million reads of an EDGE library prepared from RNA of a black spot or yellow background area of cheetah skin. The genes shown here were chosen based on their roles in pigment cell biology; six are well-established melanocyte transcriptional targets downstream from MC1R signaling (Kobayashi et al 1995;Lamoreux et al 1995;Chintala et al 2005;April and Barsh 2006;Le Pape et al 2009); four encode secreted factors that act upstream, either as ligands or to modify ligands of the MC1R Enshell-Seijffers et al 2008;Kaelin et al 2008); and one, MITF, encodes a transcription factor required for melanocyte development (Steingrímsson et al 2006). The expected direction, increase (+) or decrease (À), for expression level change of each gene is given according to when pigment production switches from yellow pheomelanin to black eumelanin.…”

Skin Pigmentation and Melanoma Risk

“…Others, such as microphthalmia (MITF) or Kit ligand (KITLG) control melanocyte migration and development (Fleischman et al, 1991;Giebel and Spritz, 1991;Tassabehji et al, 1994}. With the exception of tyrosinase, defects in melanin biosynthetic enzymes generally lead to dilutional pigmentary effects whereas defects that result in defective melanocyte survival or development result in more profound phenotypes such as piebaldism. Many pigmentation genes were identified through detailed study of coat color mutations in mice and other model organisms (Steingrimsson et al, 2006). Tyrosinase deficiency underlies oculocutaneous albinism type I (OCA1) wherein melanocytes are present in normal numbers and distribution in the skin but they fail to make any melanin pigments at all.…”