Production of congenic mouse strains carrying NOD-derived diabetogenic genetic intervals: An approach for the genetic dissection of complex traits

M. A. Yui, K. Muralidharan, B. Moreno-Altamirano, G. Perrin, K. Chestnut, E. K. Wakeland

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Insulin-dependent (Type 1) diabetes (IDD) in the NOD mouse is inherited as a complex polygenic trait making the identification of susceptibility genes difficult. Currently none of the non-MHC IDD susceptibility genes in NOD have been identified. In this paper we describe the congenic mouse approach that we are using for the dissection of complex traits, such as IDD. We produced a series of six congenic strains carrying NOD-derived diabetogenic genomic intervals, which were previously identified by linkage analysis, on a resistant background. These congenic strains were produced for the purpose of characterizing the function of each of these genes, alone and in combinations, in IDD pathogenesis and to allow fine mapping of the NOD IDD susceptibility genes. Histological examination of pancreata from 6 to 8-month-old congenic mice reveals that intervals on Chromosomes (Chrs) 1 and 17, but not 3, 6, and 11, contain NOD-derived genes that can increase the trafficking of mononuclear cells into the pancreas. Insulitis was observed only very rarely, even in older congenic mice, indicating that multiple genes are required for this phenotype. These results demonstrate the utility of this congenic approach for the study of complex genetic traits.

Original languageEnglish (US)
Pages (from-to)331-334
Number of pages4
JournalMammalian Genome
Volume7
Issue number5
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Genetics

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