TY - JOUR
T1 - Localization of a novel chromosome 7 locus that suppresses development of N‐methyl‐N‐nitrosourea—induced murine thymic lymphomas
AU - Angel, Joe M.
AU - Morizot, Donald C.
AU - Richie, Ellen R.
PY - 1993
Y1 - 1993
N2 - N‐Methyl‐N‐nitrosourea (MNU) is a potent carcinogen that causes the development of murine thymic lymphomas. MNU‐induced tumor incidence varies considerably among different inbred mouse strains. In particular, the AKR strain is highly susceptible, whereas the C57L strain is highly resistant to MNU‐induced lymphoma formation. Crosses between AKR and C57L mice were established to investigate the genetic basis for the differential susceptibility of these inbred strains. A strong association between MNU‐induced lymphoma development and coat color was observed in (AKR x C57)F2 and AKR x (AKR x C57)F1 progeny such that albino mice developed a higher tumor incidence than nonalbino animals. These data suggest that a locus on chromosome 7 influences tumor development. Analysis of four additional polymorphic loci (D7Rp2, Fes, Hbb, and Int‐2) on chromosome 7 in AKR x (AKR x C57)F1 backcross mice revealed a significant linkage between high tumor incidence and homozygous inheritance of AKR alleles at the albino (tyrosinase) and Hbb loci. Thus, inheritance of at least one C57L allele at the albino or Hbb loci was associated with protection against MNU‐induced lymphoma development. There was no association between tumor incidence and genotype at the D7Rp2, Fes, or Int‐2 loci. Taken together, the data suggest that whereas C57L mice contain a dominant tumor suppressor gene on chromosome 7, in the AKR strain both alleles at this locus are defective resulting in enhanced susceptibility to MNU‐induced lymphomagenesis.
AB - N‐Methyl‐N‐nitrosourea (MNU) is a potent carcinogen that causes the development of murine thymic lymphomas. MNU‐induced tumor incidence varies considerably among different inbred mouse strains. In particular, the AKR strain is highly susceptible, whereas the C57L strain is highly resistant to MNU‐induced lymphoma formation. Crosses between AKR and C57L mice were established to investigate the genetic basis for the differential susceptibility of these inbred strains. A strong association between MNU‐induced lymphoma development and coat color was observed in (AKR x C57)F2 and AKR x (AKR x C57)F1 progeny such that albino mice developed a higher tumor incidence than nonalbino animals. These data suggest that a locus on chromosome 7 influences tumor development. Analysis of four additional polymorphic loci (D7Rp2, Fes, Hbb, and Int‐2) on chromosome 7 in AKR x (AKR x C57)F1 backcross mice revealed a significant linkage between high tumor incidence and homozygous inheritance of AKR alleles at the albino (tyrosinase) and Hbb loci. Thus, inheritance of at least one C57L allele at the albino or Hbb loci was associated with protection against MNU‐induced lymphoma development. There was no association between tumor incidence and genotype at the D7Rp2, Fes, or Int‐2 loci. Taken together, the data suggest that whereas C57L mice contain a dominant tumor suppressor gene on chromosome 7, in the AKR strain both alleles at this locus are defective resulting in enhanced susceptibility to MNU‐induced lymphomagenesis.
KW - Lymphomagenesis
KW - chromosome mapping
KW - tumor suppressor gene
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U2 - 10.1002/mc.2940070305
DO - 10.1002/mc.2940070305
M3 - Article
C2 - 8098217
AN - SCOPUS:0027289571
SN - 0899-1987
VL - 7
SP - 151
EP - 156
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 3
ER -