International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 70 - DEVELOPMENT OF A MOUSE IMMUNOARRAY AND ITS APPLICATION TO THE ANALYSIS OF TYPE 1 DIABETES SUSCEPTIBILITY IN THE NOD MOUSE

PA Lyons
University of Cambridge

1) Kingsnorth AJ, 1) Mahadevan M, 1) Tomkies VS, 1) Morris GAJ, 2) Williams DJ, 2) Williams G, 2) Freeman T
1) University of Cambridge, 2) MRC HGMP-Resource Centre

Congenic strain analysis has proved a powerful tool in the dissection of susceptibility to type 1 diabetes in the NOD mouse.  Using this approach a number of diabetes susceptibility (Idd) loci have been mapped to intervals small enough for systematic gene identification.  Combining congenic mapping and microarray-based gene expression profiling will not only facilitate the identification of the genes underlying individual Idd loci but may also provide insight into the pathways they control.  A better understanding of the molecular events that initiate and drive disease progression is essential for the development of new drug therapies.Given the autoimmune nature of type 1 diabetes we have developed a mouse immunoarray, using spotted 50mer oligonucleotides as probes.  Genes for inclusion on the array were selected in the following manner.  Using the Gene Ontology hierarchies, 1137 genes were identified from the Mouse Genome Database on the basis of being annotated as involved in either the immune response or transcriptional regulation.  In addition, 1298 ESTs expressed in lymphoid-derived cDNA libraries were picked from dbEST.  The immunoarray has been used to determine gene expression in T cells following differentiation in vitro down either the Th1 or Th2 pathway.  Polarised T cells from NOD, the diabetes resistant NOD congenic strains, NOD.Idd3R450, NOD.Idd5R444, NOD.Idd9R1 and NOD.Idd3Idd5, as well as the parental B6 strain were profiled.  Using a statistical approach we have identified a number of differentially expressed genes between NOD and the panel of congenic strains which are the subject of follow up analysis.


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