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Radiat Res. 2010 Feb;173(2):158-64. doi: 10.1667/RR1855.1.

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.

Author information

1
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai-shi, Osaka 599-8570, Japan. morin@b.s.osakafu-u.ac.jp

Abstract

BALB/c mice are sensitive to radiation-induced lymphomagenesis, while STS mice are resistant. Using 219 [(BALB/c x STS)F(1) x BALB/c] (N2C) and 197 [(BALB/c x STS)F(1) x 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 F(2) 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.

PMID:
20095847
DOI:
10.1667/RR1855.1
[Indexed for MEDLINE]

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