Genetic basis of sex-specific resistance to neuro-oncogenesis in (BDIX×BDIV) F2 rats

Genetic basis of sex-specific resistance to neuro-oncogenesis in (BDIX×BDIV) F2 rats The identification of cancer susceptibility- and resistance-mediating genes is an essential prerequisite for prevention and early diagnosis of malignant tumors. Model organisms are helpful to identify variant alleles involved in pathways affecting individual cancer risk. BDIX and BDIV rats of both sexes are highly susceptible and resistant, respectively, to the development of N-ethyl-N-nitrosourea (ENU)-induced malignant peripheral nerve sheath tumors (MPNST), predominantly in the trigeminal nerves. Nevertheless, female (BDIV × BDIX) F2 intercross rats have a lower MPNST incidence and a longer latency time than males. Six of seven autosomal gene loci (Mss1-Mss7) controlling genetic susceptibility and resistance in (BDIV × BDIX) F2 hybrids exert allele- and sex-specific effects on tumor incidence and/or latency time of variable strength. Homozygous BDIV alleles at Mss4 or Mss7 located on rat chromosomes 6 and 10, respectively, are sufficient to cause almost complete resistance to ENU-induced MPNST development in female F2 rats regardless of the genotype of the other locus. Both loci display only weak effects on male cancer risk. Survival curves of ENU-treated F2 females depleted of animals with homozygous BDIV alleles at Mss4 and Mss7 are not significantly different from those of males, suggesting that these loci account mainly for the excess tumor resistance observed in female F2 rats. By haplotype analysis Mss4 and Mss7 could be narrowed down to 20 and 12 Mb, respectively, providing a basis for the positional identification of candidate genes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Genetic basis of sex-specific resistance to neuro-oncogenesis in (BDIX×BDIV) F2 rats

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Publisher
Springer Journals
Copyright
Copyright © 2009 by Springer Science+Business Media, LLC
Subject
Life Sciences; Zoology ; Anatomy ; Cell Biology
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-009-9226-1
Publisher site
See Article on Publisher Site

Abstract

The identification of cancer susceptibility- and resistance-mediating genes is an essential prerequisite for prevention and early diagnosis of malignant tumors. Model organisms are helpful to identify variant alleles involved in pathways affecting individual cancer risk. BDIX and BDIV rats of both sexes are highly susceptible and resistant, respectively, to the development of N-ethyl-N-nitrosourea (ENU)-induced malignant peripheral nerve sheath tumors (MPNST), predominantly in the trigeminal nerves. Nevertheless, female (BDIV × BDIX) F2 intercross rats have a lower MPNST incidence and a longer latency time than males. Six of seven autosomal gene loci (Mss1-Mss7) controlling genetic susceptibility and resistance in (BDIV × BDIX) F2 hybrids exert allele- and sex-specific effects on tumor incidence and/or latency time of variable strength. Homozygous BDIV alleles at Mss4 or Mss7 located on rat chromosomes 6 and 10, respectively, are sufficient to cause almost complete resistance to ENU-induced MPNST development in female F2 rats regardless of the genotype of the other locus. Both loci display only weak effects on male cancer risk. Survival curves of ENU-treated F2 females depleted of animals with homozygous BDIV alleles at Mss4 and Mss7 are not significantly different from those of males, suggesting that these loci account mainly for the excess tumor resistance observed in female F2 rats. By haplotype analysis Mss4 and Mss7 could be narrowed down to 20 and 12 Mb, respectively, providing a basis for the positional identification of candidate genes.

Journal

Mammalian GenomeSpringer Journals

Published: Oct 6, 2009

References

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