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PMID: 11113205 Published · ppublish English Journal Article

Efficiency alleles of the Pctr1 modifier locus for plasmacytoma susceptibility.

Molecular and cellular biology ·Vol. 21 ·No. 1 ·2001-01-00 ·Pages 310-8

Zhang SL, DuBois W, Ramsay ES, Bliskovski V, Morse HC, Taddesse-Heath L, Vass WC, DePinho RA, Mock BA

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.

MeSH Terms
3T3 Cells Alleles Animals Carrier Proteins/genetics Cell Division Cell Transformation, Neoplastic/chemically induced,genetics,pathology Chromosome Mapping Cyclin-Dependent Kinase Inhibitor p16 Flow Cytometry G1 Phase Genes, p16/genetics Genes, ras/genetics Genetic Predisposition to Disease/genetics Genetic Variation/genetics Histocytochemistry Mice Mice, Congenic Mice, Inbred BALB C Mice, Inbred DBA Mice, Knockout Plasmacytoma/chemically induced,genetics,pathology Proteins/genetics Terpenes/pharmacology Tumor Stem Cell Assay Tumor Suppressor Protein p14ARF
Chemicals
Carrier Proteins Cyclin-Dependent Kinase Inhibitor p16 Proteins Terpenes Tumor Suppressor Protein p14ARF pristane
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zhang S L
Laboratory of Genetics, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
DuBois W
Ramsay E S
Bliskovski V
Morse H C
Taddesse-Heath L
Vass W C
DePinho R A
Mock B A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.1.310-318.2001
Published
2001-01-00
Pages
310-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC88804
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.21.1.310-318.2001 PMC Full Text View journal details
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