Multiple genetic loci modify susceptibility to plasmacytoma-related morbidity in E(mu)-v-abl transgenic mice

Abstract

There is a great difference in susceptibility to v-abl transgene-induced plasmacytoma between the BALB/cAn and the relatively resistant C57BL/6J mouse strains. We have used the Mapmaker/SURVIVOR algorithm to analyze genome-wide scans on over 800 transgenic F2 hybrid mice, and have mapped at least six loci on chromosomes 2, 4, 11, 17, and 18 that modify tumor-related morbidity. As in human multiple myeloma, males were found to be more prone to plasmacytomagenesis. Different loci influence tumor susceptibility in male and female mice. Survival in females may be largely controlled by a pair of interacting loci on chromosomes 2 and 17.

Fig 1.

Comparison of survival of transgenic males and females of C.abl40 (BALB/c background, 88 mice), B6.abl40 (C57BL/6 background, 88 mice), 142 CBF1, and the first cohort of 332 CBF2 mice.

Fig 2.

Comparison of survival among 332 abl40-transgenic CBF2 generation mice in the first cohort stratified by parental origin of the transgene.

Fig 3.

Comparison of survival of subgroups of the second cohort of 509 abl40-transgenic CBF2 mice stratified by time spent in SPF conditions and the first cohort of F₂ mice. (Upper) Survival curves for the male mice. (Lower) Survival curves for the female mice.

Fig 4.

Linked autosomal loci and associated survival phenotypes in 835 abl40-transgenic CBF₂ mice. (A) Chromosomal scans for the five linked autosomes (centromere at left). LOD scores for all of the mice together as well as after stratification by sex are shown. Selected Mit markers are indicated along each chromosome. (B) Survival curves at the most tightly linked markers. Each graph shows three survival curves, one for each of the possible genotypes. Three graphs are shown for each marker, taking all of the mice together, and each sex separately.

Fig 5.

Survival of female abl40-transgenic CBF₂ animals after stratification at both D17Mit87 and D2Mit148 to show the effects of the interaction between these two markers. “A” represents BALB/c homozygosity, “H” represents heterozygosity, and “B” represents C57BL/6 homozygosity.