Fine-Mapping of the Mouse T Lymphocyte Fraction (Tlf) Locus on Chromosome 9: Association with Autoimmune Diabetes

Abstract

Tlf (T lymphocyte fraction) defines a locus that governs the unusually high fraction of circulating T lymphocytes in the nonobese diabetic (NOD) mouse. We previously mapped Tlf to proximal Chromosome 9 in BC1 mice.^[1] Here, Tlf was fine-mapped on Chromosome 9 using 8 markers covering the 43 cM interval from D9Mit90 at 9 cM to D9MU35 at 52 cM. Markers for diabetic genes on Chromosomes 3, 4, 5, 6, and 17 were also examined for effects on the Tlf phenotype. By both parametric and nonparametric tests, Tlf associated with two areas on Chromosome 9, one with the segment bounded by D9MU66 (15 cM) and D9MU2 (17 cM) and a second region near D9MU7I (29 cM). This linkage pattern was observed both in BC1 and F2 populations. Thus, the Tlf phenotype is possibly governed by two genes on Chromosome 9. An influence by sex on the penetrance of Tlf was evident in that linkage was strongest for female F2 mice and male BC1 mice. One locus controlling the T lymphocyte fraction may be Idd2 since historically a subline of NOD mice with a low T cell fraction showed a low incidence of diabetes. Candidate genes for Tlf are Ets1 and Fli1, proximally and Igif distally.

Key Words:

• Diabetes
• Idd2
• nonobese diabetic mouse
• Tlf
• Igif
• apoptosis