Functional genomic analysis of the NKT cell control locus Nkt1 and the Bana3/Babs2 lupus susceptibility locus

Funded Activity Summary

The major populations of white blood cells responsible for learned immunity are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body's own tissues, resulting in autoimmune diseases such as lupus, in which antibodies are deposited in the tissues causing inflammation in organs such as the brain, skin and especially the kidneys. Another population of white blood cells, termed NKT cells, plays an important role in keeping the T and B cells in check, and we have found that these cells are deficient in an inbred mouse strain, NOD mice, which develop lupus after exposure to a particular type of bacteria, called mycobacteria. We have found that one of the major genes conferring susceptibility to lupus in these mice lies in the same genetic region as the major gene controlling NKT cell numbers, raising the possibility that the deficiency in NKT cells in this strain predisposes it to developing lupus. The experiments proposed for this project are divided into two groups. The first group test whether increasing NKT cell numbers by either injecting them, or else transferring genes that allow more to develop naturally, can affect the risk of developing lupus. The second group of experiments examine the potential roles of two specific genes which are in the genetic region of interest, and which we think might control both NKT cell numbers and lupus susceptibility. The approach to be used involves sophisticated techniques of genetic analysis, such as the use of mutant mice which carry genetic mutations near the relevant genes, and congenic mice, which are like NOD mice, but carry in addition to NOD genes, genetic regions from a non-autoimmune strain.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $235,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Clinimetrics

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Autoimmunity | Disease gene | Immunoregulation | haemolytic anaemia | systemic lupus erythematosus | type 1 diabetes

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