Document Type

Thesis - Open Access

Award Date


Degree Name

Master of Science (MS)

Department / School



The study of spontaneous or induced genetic anomalies has been of considerable benefit to cellular and molecular biology. By observing abnormal developmental processes resulting from genetic mutations, we can come to a better understanding of normal mechanism of gene action. The complex I-locus of autosome IX of the house mouse, Mus musculus, represents an outstanding developmental and genetic system to investigate the control of early mammalian differentiation. This locus, which apparently extends over some length of chromosome IX, appears to participate in functions concerned with early developmental. processes in the embryo. Many lethal, as well as viable all alleles, are found at this locus. The time and cellular site of the earliest recognizable activity are known for several which are lethal in the hon1ozygous condition. More than 75 recessive alleles at this locus have thus far been identified. The allele showing the earliest developmental effects is the t12 which, in fact, represents the earliest acting of any known mammalian lethal gene. Embryos homozygous for t12 develop normally through the rnorula stage but fail to develop into functional blastocysts. Some embryos, however, begin to show phenotypic effects as early as the 4 to 8-cell stage. Several factors facilitate the study of I-locus activity during early embryogenesis in mice. A balanced lethal line of mice can easily be maintained, because both homozygous conditions (T/T and t 12/t 12) are lethal. The homozygous dominant T/T was shown to be lethal at about 10-11 days, while the -homozygous recessive t12/t1 2 undergoes developmental arrest at 3-4 days. Thus only the heterozygous condition T/t 12 proves viable and maintains the balanced line. Also of importance is the fact that while heterozygous females produce T and t12 alleles at the predictable Mendelian ratio of 1:1, the males show a segregation distortion favoring the transmission of the lethal t12. The transmission frequency of the t 1 2 allele in heterozygous males has been shown to be quite variable from 73 percent to 90 percent averaging about 76 percent. It is the purpose of this study to provide add additional information on the mechanism of lethality of the t 12/t 12 genotype. Mouse embryos homozygous for t 12 undergo developmental arrest at the morula stage. In an attempt to explain the observed lethality, many biochemical and morphological abnormalities of the t 12/t 12 embryo have been described. However, the primary genetic defect remains obscure. Information resulting from this study will be important to our understanding of the mechanism of gene action during early cellular. differentiation in the mammalian embryo. In view of the many congenital malformations in man which are genetically controlled, research in this field is of considerable interest.

Library of Congress Subject Headings


Variation (Biology)


South Dakota State University Theses



Number of Pages



South Dakota State University