International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

Table of Contents * Genes, Physical Mapping and Sequencing * Gene Identification * Bioinformatics * Common Resources * RIKEN Session * Functional Genomics * Complex Traits * Mutagenesis * Developmental Genetics and Differentiation * Verne Chapman Memorial Lecture I and II

B28. The Genetics of Susceptibility to Mouse Plasmacytomagenesis

Rebecca A. Liddell¹, Wendy DuBois¹, Marianne K. Henderson¹, Hiroyuki Aburatani², David Housman² and Beverly A. Mock^1
1NCI, Bldg. 37, Rm 2B08, NIH, Bethesda, MD 20892-4255 and ²MIT, Cambridge, MA 02139

Mouse plasmacytomas share several pathogenetic features common to both human multiple myeloma and Burkitt's lymphoma. The neoplastic processes of plasmacytomagenesis are the result of a complex sequence of genetic events. The mouse model system employed by our laboratory provides a powerful tool for studying the genetic basis of tumor initiation, promotion and progression to malignant disease. Intercross, backcross and congenic strain analyses have indicated that at least three, and potentially more, genes are involved in tumor formation in susceptible BALB/cAnPt mice as compared to resistant DBA/2n mice. These results indicate that plasma cell tumorigenesis is a complex genetic trait. Three previously identified loci, Pctr1, 2, and 3 reside on mouse Chr 4 in regions of the mouse genome that share extensive linkage homology with human Chr 1p32-31 and 1p36, respectively. A second approach adopted in our laboratory to identify tumor susceptibility/resistance genes, was representational difference analysis, or RDA. This PCR based, subtractive DNA hybridization protocol helped isolate markers closely linked to the tumor resistant phenotype using DNAs from one of our more resistant congenic strains. Congenic mice positive for the RDA-derived markers were tested for their tumor susceptibility/resistance phenotype. This process has identified a new candidate locus, Pctr4, that maps to mouse Chr 2.