title: Efficiency alleles of the Pctr1 modifier locus for plasmacytoma susceptibility.
abstract: The susceptibility of BALB/c mice to pristane-induced plasmacytomas is a complex genetic trait involving multiple loci, while DBA/2 and C57BL/6 strains are genetically resistant to the plasmacytomagenic effects of pristane. In this model system for human B-cell neoplasia, one of the BALB/c susceptibility and modifier loci, Pctr1, was mapped to a 5.7-centimorgan (cM) chromosomal region that included Cdkn2a, which encodes p16(INK4a) and p19(ARF), and the coding sequences for the BALB/c p16(INK4a) and p19(ARF) alleles were found to be polymorphic with respect to their resistant Pctr1 counterparts in DBA/2 and C57BL/6 mice (45). In the present study, alleles of Pctr1, Cdkn2a, and D4Mit15 from a resistant strain (BALB/cDAG) carrying DBA/2 chromatin were introgressively backcrossed to the susceptible BALB/c strain. The resultant C.DAG-Pctr1 Cdkn2a D4Mit15 congenic was more resistant to plasmacytomagenesis than BALB/c, thus narrowing Pctr1 to a 1.5-cM interval. Concomitantly, resistant C57BL/6 mice, from which both gene products of the Cdkn2a gene have been eliminated, developed pristane-induced plasma cell tumors over a shorter latency period than the traditionally susceptible BALB/cAn strain. Biological assays of the p16(INK4a) and p19(ARF) alleles from BALB/c and DBA/2 indicated that the BALB/c p16(INK4a) allele was less active than its DBA/2 counterpart in inducing growth arrest of mouse plasmacytoma cell lines and preventing ras-induced transformation of NIH 3T3 cells, while the two p19(ARF) alleles displayed similar potencies in both assays. We propose that the BALB/c susceptibility/modifier locus, Pctr1, is an "efficiency" allele of the p16(INK4a) gene.
authors: Laboratory of Genetics, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: S L
authors: SL
authors: Zhang
authors: W
authors: W
authors: DuBois
authors: E S
authors: ES
authors: Ramsay
authors: V
authors: V
authors: Bliskovski
authors: H C
authors: HC
authors: Morse
authors: L
authors: L
authors: Taddesse-Heath
authors: W C
authors: WC
authors: Vass
authors: R A
authors: RA
authors: DePinho
authors: B A
authors: BA
authors: Mock
mesh_terms: D016475:3T3 Cells; D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D002874:Chromosome Mapping; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005434:Flow Cytometry; D016193:G1 Phase; D019942:Genes, p16 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006651:Histocytochemistry; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010954:Plasmacytoma / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics; D013729:Terpenes / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay; D025803:Tumor Suppressor Protein p14ARF
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011506:Proteins; D013729:Terpenes; D025803:Tumor Suppressor Protein p14ARF; C009042:pristane