Sequence Variation and Expression of theGimapGene Family in the BB Rat

[摘要] Positional cloning of lymphopenia (lyp) in the BB rat revealed a frameshift mutation inGimap5, a member of at least seven related GTPase Immune Associated Protein genes located on rat chromosome 4q24.Our aim was to clone and sequence the cDNA of the BB diabetes prone (DP) and diabetes resistant (DR) alleles of all sevenGimapgenes in the congenic DR.lyprat line with 2 Mb of BB DP DNA introgressed onto the DR genetic background.All (100%)DR.lyp/lyprats are lymphopenic and develop type 1 diabetes (T1D) by 84 days of age whileDR.+/+rats remain T1D andlypresistant.Among the sevenGimapgenes, theGimap5frameshift mutation, a mutant allele that produces no protein, had the greatest impact on lymphopenia in theDR.lyp/lyprat.Gimap4andGimap1each had one amino acid substitution of unlikely significance for lymphopenia. Quantitative RT-PCR analysis showed a reduction in expression of all sevenGimapgenes inDR.lyp/lypspleen and mesenteric lymph nodes when compared toDR.+/+.Only four;Gimap1,Gimap4,Gimap5, andGimap9were reduced in thymus.Our data substantiates theGimap5frameshift mutation as the primary defect with only limited contributions to lymphopenia from the remainingGimapgenes.

[学科分类] 内分泌与代谢学