CHROMOSOMAL FRAGILITY IN MICE (CYTOGENETICS, ANIMAL MODELS, 5-FLUORODEOXYURIDINE, NUCLEOLAR ORGANIZERS)
A variety of chromosomal fragile sites has been observed on human chromosomes. Thus far, only one of the 25 fragile sites has been found to be related to any disorder. The specific requirements for fragile site expression may explain why, in addition to humans, only one laboratory animal has been shown to exhibit chromosomal fragility. Lymphocytes and fibroblast-like cell cultures from two inbred strains of mice were treated with 5-fluorodeoxyuridine (FUdR) in order to induce chromosomal lesions. Short-term peripheral blood cultures of strains AEJ/GnRk, RBC/Dn and CASA/Rk were exposed to 0.0, 0.05, 0.1 and 0.4 uM FUdR for 24 hours. Chromosome preparations were homogeneously stained with Giemsa. Slides were coded and cells were scored blindly for gaps, breaks and exchange figures. Several kinds of chromosomal lesions, including bi- and triradial exchange figures, were observed in the FUdR-treated cultures from each strain. Primary lung fibroblast-like cells of strains AEJ/GnRk and RBC/Dn were treated with 0.0, 1.0 and 10.0 uM FUdR for 24 hours. After fixation and slide preparation, cells were stained using a Giemsa-trypsin banding technique. Slides were coded and cells were scored blindly for gaps, breaks and exchange figures. These lesions were recorded by chromosome band. Fragile sites were defined as a gap, break and an exchange figure observed repeatedly at the same point on the chromosome in cells from more than one animal per strain. It was noted that the number of observed chromosomal lesions increased with increased concentrations of FUdR. In addition, statistical analysis demonstrated that FUdR caused non-site-specific damage along the linear axis of some chromosomes in both strains of mice. Further analysis indicated strain specificity for both "hot" chromosomes as well as specific fragile sites. Analysis of 735 cells identified 3 constitutive fragile sites, 12A2, 15A2 and 18A2 for strains RBC/Dn and AEJ/GnRk, and one strain-specific heritable fragile site, 19B, for strain AEJ/GnRk. These fragile sites are located within the nucleolar organizer regions. Potential fragile sites were observed at bands 1B and 9B for AEJ/GnRk and at 1H1, 2H1, 8A4, 9A2, 17B, 17E4, 18C, 19B and 19C2 for RBC/Dn. Results from this study have shown that fragile sites can be induced and observed in the mouse genome. Fragile sites provide new polymorphic markers that can be used in comparative genetic and cytological identification of the assignment of genes to specific chromosomal bands. In addition, mouse fragile sites may serve as experimental models for the study of the nature of chromosomal fragility.
SANZ, MAUREEN MESIS, "CHROMOSOMAL FRAGILITY IN MICE (CYTOGENETICS, ANIMAL MODELS, 5-FLUORODEOXYURIDINE, NUCLEOLAR ORGANIZERS)" (1985). ETD Collection for Fordham University. AAI8521416.