Document Type

Thesis - Open Access

Award Date


Degree Name

Master of Science (MS)



First Advisor

Nels H. Granholm Ph. D.


The lethal yellow gene (Ay) located on chromosome two of the mouse (Mus musculus) represents the top dominant of the agouti series. It was first described by Cuenot in 1905 as being lethal in the homozygous (Ay/Ay) state. These (Ay/Ay) embryos encounter abnormalities at the morula or blastocyst stage and die early during the sixth day of gestation when the trophectoderm comes in contact with the uterine epithelium at implantation. Other abnormalities of the Ay gene besides the yellow coat color include its association with the stimulation of normal body growth, obesity, a diabetes like syndrome and sterility. In addition to these pleiotropic effects, the Ay gene has been associated with increased susceptibility to both spontaneous and induced pulmonary tumors and other cancers. Since genetic mutations can often afford the scientist the ability to study and learn how normal systems operate, the lethal yellow gene (Ay) enables one to study any number of its pleiotropic effects. In order to study the primary genetic lesion of the (Ay) gene, the earliest acting pleiotropic effect, namely coat color, can be studied. The action of AY on follicular pigment cells enables one to study genetic regulation of cellular differentiation. The pathways of pigment granule formation in hair bulb pigment cells differ both morphologically and biochemically between the (Ay) nonagouti black (control) and the lethal yellow (Ay/a) mouse. The accurate characterization of the differences in the morphogenesis of pigment granules in genetically black (a/a) versus yellow (Ay/a) hair bulb pigment cells serves as one focus of this thesis. These morphogenetic studies utilized the transmission electron microscope to provide information pertaining to four different genetic mutants. These four genotypes were normal nonagouti (a/a), lethal yellow (Ay/a), the yellow albino (Ay/a; c2J/c2J), and black albino (a/a; c2J/c2J). The double mutant albinos (Ay/a; c2Jj/c2J and a/a; c2J/c2J) were analyzed to study the genetic interaction that occurred between agouti and albino loci. Tyrosinase is a major enzyme in several of the steps in the Mason-Raper pathway which begins with the simple amino acid, tyrosine and ends with a complex polymer, eumelanin. Electrophoretic studies were performed to characterize various multiple molecular forms of tyrosinase in lethal yellow (Ay/a) and nonagouti (a/a) mice. The objectives of this study were twofold. One objective was to characterize the morphogenesis of hair follicle pigment granules in four different genotypes of agouti and albino locus mutants in order to elucidate how nonagouti (a), lethal yellow (A/y) and albino (c2J) genes affect the program of granule ontogeny. The second objective was to learn how the pattern of tyrosinase synthesis, processing and deployment was altered, changed or modulated by nonagouti (a)J lethal yellow (Ay) and albino (c2J) genes.

Library of Congress Subject Headings

Lethal mutation

Mice -- Genetics


South Dakota State University Theses



Number of Pages



South Dakota State University