Low-penetrance genetic susceptibility and resistance loci implicated in the relative risk for radiation-induced acute myeloid leukemia in mice.
Inbred CBA/H mice are susceptible to radiation-induced acute myeloid leukemia (r-AML), and C57BL/6 mice are resistant. A genome-wide screen for linkage between genotype and phenotype (r-AML) of 67 affected (CBA/H x C57BL/6)F1 x CBA/H backcross mice has revealed at least 2 suggestive loci that contribute to the overall lifetime risk for r-AML. Neither is necessary or sufficient for r-AML, but relative risk is the net effect of susceptibility (distal chromosome 1) and resistance (chromosome 6) loci. An excess of chromosome 6 aberrations in mouse r-AML and bone marrow cells up to 6 months after irradiation in vivo suggests the locus confers a proliferative advantage during the leukemogenic process. The stem cell frequency regulator 1 (Scfr1) locus maps to distal chromosome 1 and determines the frequency of hemopoietic stem cells (HSCs) in inbred mice, suggesting that target size may be one factor in determining the relative susceptibility of inbred mice to r-AML.
Boulton
Emma
E
Department of Genetics and the MRC Toxicology Unit, University of Leicester, United Kingdom.
Cole
Clare
C
Knight
Abigail
A
Cleary
Helen
H
Snowden
Roger
R
Plumb
Mark
M
D000818:Animals; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007178:Inbreeding; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D019683:Penetrance; D012306:Risk