Development of iNKT cells: influence of Y-chromosome genes (153.44)

Abstract

Abstract In previous studies, we identified a mouse strain, B6.Ynkt, in which only males were deficient in iNKT cells and demonstrated that the deficiency was linked to Y-chromosome factors. We reasoned that the deficiency could be due to either a consomic effect of the Y-chromosome or due to a spontaneous germ line mutation on the Y- chromosome that occurred during the backcross to B6 background. To test the consomic hypothesis, we examined the iNKT cell frequency and number, in 16 different Y consomic strains. Although there is variation between the different strains tested none of them have a drastic decrease in iNKT cell number and frequency. To test the second hypothesis, we performed µarray on residual iNKT cells and conventional CD4+ T cells from the B6.Ynkt strain. The gene expression profile from these cells was compared to B6 iNKT cells and CD4+ T cells. We found that 4 contiguous genes on the Y-chromosome, were not expressed in the B6.Ynkt iNKT cells but were expressed in wild-type B6 iNKT cells. Importantly, these genes were expressed similarly in conventional CD4+ T cells from both wild-type B6 and B6.Ynkt mice suggesting the phenotype observed was not due to a deletion in this area. Genomic analysis confirmed that these 4 genes are present in both strains of mice. Taken together, our results argue against a consomic effect. Rather the data revealed a possible genetic expression repression of specific genes found contiguously on the Y-chromosome.