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Nucleic Acids Research, 2002, Vol. 30, No. 6 1394-1400
© 2002 Oxford University Press

Representational difference analysis in a lupus-prone mouse strain results in the identification of an unstable region of the genome on chromosome 11

Guoliang Fu, Michelle E. K. Haywood and Bernard J. Morley*

Rheumatology Section, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 ONN, UK

BXSB mice develop a lupus-like autoimmune syndrome. We have previously identified several intervals that were linked to disease and, in an attempt to characterise lupus susceptibility genes within these intervals, we have sought to isolate differentially expressed genes. Representational difference analysis was used to compare gene expression between BXSB and C57BL/10 mice using spleen and thymus as a source of mRNA. The majority of differentially expressed sequences identified were immunoglobulin and gp70-related sequences, overexpression of these being characteristic of the disease. Among other isolated sequences were a sialyltransferase gene, a mouse tumour virus superantigen gene (Mtv-3), and the virus-related sequence, hitchhiker. In BXSB the sialyltransferase gene not only overexpressed spliced transcripts, but also produced high levels of unspliced mRNA. Further analysis demonstrated that the copy number of the three linked sequences: sialyltransferase, Mtv-3 and hitchhiker, was amplified in BXSB and that the structural organisation of this locus varies in different mouse strains. This locus consists of three parts, Mtv-3–hitchhiker–sialyltransferase, hitchhiker–sialyltransferase, and sialyltransferase alone. Different combinations of the regions are present in different mouse strains. Linkage analysis demonstrated that this region at the distal end of chromosome 11 is weakly linked to phenotypic markers of disease.

* To whom correspondence should be addressed. Tel: +44 20 8383 2353; Fax: +44 20 8743 3109; Email: b.morley{at}ic.ac.uk Present address:Guoliang Fu, Institute of Molecular and Cell Biology, The National University of Singapore, 30 Medical Drive, Singapore 117609


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