A Retroviral Insertion in the Dilute (d) Locus Provides Molecular Access to This Region of Mouse Chromosome 9

This chapter discusses the genetic analysis and molecular analysis of the dilute (d) locus. The original d mutation is the mutation of the fancy mouse and was among the coat-color variants first studied by mouse geneticists. This recessive mutation, when homozygous, is associated with a single phenotypic effect, a lightening of coat-color. The reduction of pigment in the coat hairs of d/d mice is not associated with a decrease in melanin synthesis, but is instead correlated with aberrant melanocyte morphology. Melanocytes isolated from mice wild-type at d display many thick dendritic processes extending from the cell and the melanin granules (melanosomess) are dispersed along these processes. In contrast, melanocytes from mice homozygous for d have few dendritic processes and most melanosomes clump around the nucleus. The abnormal melanocyte morphology is believed to inhibit proper interaction between the melanocyte and the hair bulb, resulting in an irregular distribution of melanosomes within the hair shaft and the appearance of a dilution in coat color. The chapter also presents the analysis of the d-se region of chromosome and strategies for identifying and characterizing other functional units of the d-se complex. An important step in the analysis of the d-se region of chromosome 9 is the incorporation of these mutations into tester stocks that were used in mutagenesis screens. In these screens, wild-type mice are treated with a potential mutagen (radiation or chemical) and are then crossed to a multiple-recessive tester stock homozygous for a number of phenotypic mutations including d and se.