Identification of a structurally distinct CD101 molecule encoded in the 950-kb Idd10 region of NOD mice.

Published

Journal Article

Genes affecting autoimmune type 1 diabetes susceptibility in the nonobese diabetic (NOD) mouse (Idd loci) have been mapped using a congenic strain breeding strategy. In the present study, we used a combination of BAC clone contig construction, polymorphism analysis of DNA from congenic strains, and sequence mining of the human orthologous region to generate an integrated map of the Idd10 region on mouse chromosome 3. We found seven genes and one pseudogene in the 950-kb Idd10 region. Although all seven genes in the interval are Idd10 candidates, we suggest the gene encoding the EWI immunoglobulin subfamily member EWI-101 (Cd101) as the most likely Idd10 candidate because of the previously reported immune-associated properties of the human CD101 molecule. Additional support for the candidacy of Cd101 is the presence of 17 exonic single-nucleotide polymorphisms that differ between the NOD and B6 sequences, 10 causing amino acid substitutions in the predicted CD101 protein. Four of these 10 substitutions are nonconservative, 2 of which could potentially alter N-linked glycosylation. Considering our results together with those previous reports that antibodies recognizing human CD101 modulate human T-cell and dendritic cell function, there is now justification to test whether the alteration of CD101 function affects autoimmune islet destruction.

Full Text

Duke Authors

Cited Authors

  • Penha-Gonçalves, C; Moule, C; Smink, LJ; Howson, J; Gregory, S; Rogers, J; Lyons, PA; Suttie, JJ; Lord, CJ; Peterson, LB; Todd, JA; Wicker, LS

Published Date

  • June 2003

Published In

Volume / Issue

  • 52 / 6

Start / End Page

  • 1551 - 1556

PubMed ID

  • 12765969

Pubmed Central ID

  • 12765969

Electronic International Standard Serial Number (EISSN)

  • 1939-327X

International Standard Serial Number (ISSN)

  • 0012-1797

Digital Object Identifier (DOI)

  • 10.2337/diabetes.52.6.1551

Language

  • eng