Plasmacytomas (PCTs) were induced in 47%of BALB/cAnPt mice by the intraperitoneal injection of pristane, in 2% of (BALB/c x DBA/2N)F1, and in 11% of 773 BALB/cAnPt x (BALB/cAnPt x DBA/2N)F1 N2 backcross mice. This result indicates a multigenic mode of inheritance for PCT susceptibility. To locate genes controlling this complex genetic trait, tumor susceptibility in backcross progeny generated from BALB/c and DBA/2N (resistant) mice was correlated with alleles of 83 marker loci. -5). Most other inbred strains of mice are resistant to PCT induction by these agents. The incidence of induced PCTs in backcross and recombinant inbred mice derived from resistant (R) and susceptible (S) progenitors has indicated that PCT susceptibility is under multigenic control (6-10).To localize genes involved in plasmacytomagenesis, associations of tumor susceptibility with alleles of genetic markers distributed across the mouse genome were examined in backcross progeny from a cross of S (BALB/c) and R (DBA/2) strains of mice. Our approach was similar to that used in the dissection of complex genetic traits associated with other disease processes (11)(12)(13)(14). The genotypes of the mice that developed PCTs were examined for homozygosity (C/C) at specific loci or sequence tagged sites (STSs). In this study, regions of mouse chromosome (Chr) 4 and Chr 1 have been implicated in the genetic control of plasmacytomagenesis.
MATERIALS AND METHODSTumor Induction. A panel of 821 backcross progeny was generated from a cross between 24 BALB/cAnPt (PCTsusceptible) females and 8 (BALB/cAnPt x DBA/2N)F1 (PCT-resistant) males; these mice were bred and maintained in our closed conventional mouse colony. Six-to 10-week-old mice [100 BALB/cAnPt, 100 (C x D)F1, and 773 first generation backcross progeny] were inoculated i.p. with three 0.5-ml injections of pristane (2,6,10,14-tetramethylpentadecane) on days 0, 60, and 120.The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.Diagnosis. Starting at day 134, Giemsa-stained slides of ascites smears from peritoneal exudate cells were examined on a biweekly basis for the presence of atypical plasma cells. Mice were diagnosed as PCT-positive when accumulations of 10 or more atypical plasma cells were seen in the ascites smears. At this time, ascites samples from individual tumorbearing mice were transferred i.p. to pristane-pretreated CDF1 hybrids for purposes of generating tumor tissue for viable freezing and immortalization. Host (spleen, kidney, and liver) and tumor (mesenteric oil granuloma) tissues were removed and frozen in liquid nitrogen.Marker Typing and Molecular Analyses of Tumors. DNA isolation (tumor and kidney), restriction enzyme digestion, agarose gel electrophoresis, Southern blotting, and restriction fragment length polymorphism (RFLP) analyses were performed as described (15). D4Rck clones were amplified and labeled by PCR a...