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1 February 2010 Two Loci Controlling Susceptibility to Radiation-Induced Lymphomagenesis on Mouse Chromosome 4: Cdkn2a, a Candidate for One Locus, and a Novel Locus Distinct from Cdkn2a
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Abstract

BALB/c mice are sensitive to radiation-induced lymphomagenesis, while STS mice are resistant. Using 219 [(BALB/c × STS)F1 × BALB/c] (N2C) and 197 [(BALB/c × STS)F1 × STS] (N2S) animals, we performed a genome-wide search for loci controlling susceptibility to lymphomagenesis induced by radiation. Association of markers with the survival of animals was analyzed by the log rank test. For N2C mice, a significant correlation was detected, with four markers on the proximal to mid portion of chromosome 4: D4Mit302 and D4Mit255, P  =  0.0075; D4Mit17, P  =  0.034; and D4Mit86, P  =  0.048. On the other hand, no significant linkage was detected in N2S mice. We analyzed BALB/c mice congenic for the STS allele in different regions of chromosome 4 and identified a locus with a conspicuous effect on survival located within a 7-Mb region between D4Mit302 and D4Mit144, where BALB/c mice harbor hypomorphic variant alleles of the tumor suppressor gene Cdkn2a, which encodes the cyclin-dependent kinase inhibitor protein p16INK4a. Using pooled F2 intercrosses between the BALB/c and congenic lines carrying the STS allele near D4Mit17, but not in the range from D4Mit302 to D4Mit144, we assigned the second locus to an 11.4-Mb region in the vicinity of D4Mit17. Although Cdkn2a is a likely candidate for the locus controlling susceptibility to lymphomagenesis on chromosome 4, a novel tumor susceptibility gene different from Cdkn2a exists near the primary locus.

Nobuko Mori "Two Loci Controlling Susceptibility to Radiation-Induced Lymphomagenesis on Mouse Chromosome 4: Cdkn2a, a Candidate for One Locus, and a Novel Locus Distinct from Cdkn2a," Radiation Research 173(2), 158-164, (1 February 2010). https://doi.org/10.1667/RR1855.1
Received: 11 May 2009; Accepted: 1 October 2009; Published: 1 February 2010
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