This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pataer, A. Articles by Hiai, H. Search for Related Content PubMed PubMed Citation Articles by Pataer, A. Articles by Hiai, H.

Two Dominant Host Resistance Genes to Pre-B Lymphoma in Wild-derived Inbred Mouse Strain MSM/Ms¹

Department of Pathology and Biology of Disease, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-Ku, Kyoto 606, Japan

To explore possible host genes suppressing spontaneous B-lymphomagenesis in the mouse, expression of ecotropic murine leukemia virus (E-MuLV) and lymphoma development were observed in crosses between the pre-B lymphoma-prone SL/Kh and low-lymphoma strains of mice. E-MuLV expression was intensely inhibited in F₁ hybrids with the strains either with the Fv-1^b allele (BALB/c, C57BL/10, and A/J) or with the Fv-1^nr allele (NZB). In these F₁ mice, no lymphoma developed by 18 months of age. On the other hand, F₁ hybrids with the strains with the Fv-1ⁿ allele [C3H/He, CBA/N, SJL, DBA/2, and MSM/Ms (hereafter referred to as MSM)], high or intermediate levels of E-MuLV expression were observed. Lymphoma incidence in these F₁ hybrids, however, was low. This observation suggests the presence of non-Fv-1 dominant resistance genes in these strains. In an attempt to characterize such host genes, we analyzed crosses between SL/Kh mice and a wild mouse-derived inbred strain, MSM/Ms. The latter was susceptible to N-tropic virus expression, but (SL/Kh x MSM)F₁ hybrids did not develop any lymphomas. Of 60 SL/Kh x (SL/Kh x MSM)F₁ hybrids, 14 B-lineage lymphomas, including 13 pre-B and 1 follicular center cell lymphoma, developed by 18 months of age. This was compatible with the hypothesis of two independently segregating dominant genes of MSM suppressing lymphomagenesis. By scanning all chromosomes for linkage of lymphoma susceptibility with polymorphic microsatellite loci, one significant linkage disequilibrium was found in the proximal segment of chromosome 17, containing D17MIT44 (map position 15.0) to D17MIT150 (position 33.3), and another linkage disequilibrium, in the midproximal segment of chromosome 18, containing D18MIT90 (map position 28.0) and D18MIT140 (37.0). All 13 pre-B lymphoma-bearing backcross mice were homozygous for SL/Kh-derived alleles at these loci. We named the gene on chromosome 17 MsmrI (for MSM resistance 1) and that on chromosome 18 Msmr2 (for MSM resistance 2).

¹ This study was supported by Grants-in-Aid from the Ministry of Education, Culture, and Science, from the Ministry of Health and Welfare, Japan, and from the Japanese Owner's Association.

² To whom requests for reprints should be addressed. Phone: 081-075-753-4421; Fax: 081-075-743-4432; E-mail: hiai@med.kyoto-u.ac.jp.

Received 3/13/96. Accepted 6/18/96.

This article has been cited by other articles:

				T. A. Dragani 10 Years of Mouse Cancer Modifier Loci: Human Relevance Cancer Res., June 15, 2003; 63(12): 3011 - 3018. [Abstract] [Full Text] [PDF]