• About T1DBase
• Regions
  • Human T1D Regions
  • Mouse T1D Regions
    • Linkage Regions
    • Orthologous Regions
  • Rat T1D Regions
    • Linkage Regions
    • Orthologous Regions
    • QTL Regions
• Genome Browser
  • Human GBrowse
  • Mouse GBrowse
  • Rat GBrowse
• Tools
  • Gene Dossier
  • Beta Cell Gene Atlas
  • Batch Query
  • Sequence Search
  • HaemAtlas Search
  • Mouse Strain Search
• Data
  • Poster Pages
  • Downloads
  • Data Submission
• Help
  • FAQ
  • T1DBase Tutorial
• Contact Us

The GIMAP Gene Family

Introduction
	Lymphopenia in BB rats shows a simple Mendelian mode of inheritance. A framshift mutation in the gene Gimap 5 has been shown to cause lymphopenia in BioBreeding (BBDR.lyp)1 rats (MacMurray et al.). Found on rat chromosome 4, it is tightly linked to similar genes in the GIMAP family which all contain an Avirulence Induced Gene 1 (AIG1) domain. Although Gimap 5 is known to be involved with immune system development, it is possible that other Gimap genes may contribute to lymphopenia and diabetes. Furthermore, with common protein motifs and tight clustering, the Gimap family may be similarly regulated. Here we show Gimap expression levels in wild type (+/+), heterozygous (+/lyp), and homozygous (lyp/lyp) BB rats. The Rat Gimap family contains seven novel genes: Gimap 1, Gimap 4, Gimap 5, Gimap 6, Gimap 7, Gimap 8, and Gimap 9. No orthologs to human GIMAP 2 or orthologs to mouse Gimap 3 have been found in rat. 1BBDR.lyp is from the BioBreeding Diabetes Resistant rat (with the lymphopenia locus introgressed on it) rat line, which is kept in heterozygous state so that breeding results in lyp/lyp, lyp/+ or +/+.
Experimental Setup
	Gimap gene Gimap8 Gimap9 Gimap4 Gimap6 Gimap7 Gimap1 Gimap5    Lr8    Thymus Spleen MLN Bone Marrow Kidney Figure 1: Wild-type Expression normalized to total RNA. Copies / ng
Figure 2:Gimap family gene order in Rat, chr. 4.
Methods
	Multiple Litters Multiple Litters Five rat litters were used: DF4-17, DF5-17, DF9-13, and DF10-2. DF4-17 and DF5-17 used purified PolyA+ RNA and DF9-13, DF10-2, and DF10-3 used total RNA for QPCR experiments. When normalized to total RNA, DF4-17 and DF5-17 expression ratios greatly differed from the other litters. In order to reconcile that difference and include all the litters, expression was normalized to cyclophilin. Specific pathogen-free wild-type (+/+) and heterozygous (lyp/+) DR.lyp rats have normal lymphosite numbers and do not develop diabetes, whereasDR.lyp/lyp rats have T-cell lymphopenia from birth and clinical onset of Type I diabetes between 50 to 108 days of age in 100% of the animals.(Beig et al.) Expression level raw data is first normalized by cyclophylin, then to wild-type in each litter. Click on image to View by genotype:   RNA Experiment Methods RNA Experiment Methods Quantitative PCR was performed on RNA recovered from rat tissue from five litters. Experiments were duplexed with cyclophilin and done in triplicates.   Normalization Methods Normalization Methods QPCR values were normalized to either cyclophilin or total RNA and expressed as a ratio gene copy number per ng or either cyclophilin or total RNA. Normalizing to total RNA is advantageous because total RNA levels generally stay the same in cells over different conditions. However, total RNA is primarily made of ribosomal RNA. Quantitation of ribosomal RNA does not always accurately show the effects of different experimental conditions on the expression of the genes of interest. Normalizing to a gene (in this case cyclophilin) is advantageous because the normalization gene is subject to the same experimental conditions as the genes of interest. However, the experimental conditions themselves can change the expression levels of the normalization gene. The optimal normalization gene has to be found for each experiment.
Gimap Additional Information
	Gimap Gene Family
Folders
Suggested Views
	Gimap Genes in Gene Atlas View expression in various tissues and conditions.
Related Papers:
	Gimap4 accelerates T-cell death. Schnell S, Démollière C, van den Berk P, Jacobs H Blood. 2006 PubMed ID: 16569770   Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene. MacMurray AJ, Moralejo DH, Kwitek AE, Rutledge EA, Van Yserloo B, Gohlke P, Speros SJ, Snyder B, Schaefer J, Bieg S, Jiang J, Ettinger RA, Fuller J, Daniels TL, Pettersson A, Orlebeke K, Birren B, Jacob HJ, Lander ES, Lernmark A Genome Res. 2002 PubMed ID: 12097339   Comparative analysis of the human gimap gene cluster encoding a novel GTPase family. Krücken J, Schroetel RM, Müller IU, Saïdani N, Marinovski P, Benten WP, Stamm O, Wunderlich F Gene. 2004 PubMed ID: 15474311   Comment: The Gimap7 and Gimap9 gene names differ between this publication, the UCSC Genome Browser database and the Rat Genome Nomenclature Committee. Malaria-suppressible expression of the anti-apoptotic triple GTPase mGIMAP8. Krücken J, Epe M, Benten WP, Falkenroth N, Wunderlich F J Cell Biochem. 2005 PubMed ID: 16088918   Comment: The Gimap7 and Gimap9 gene names differ between this publication, the UCSC Genome Browser database and the Rat Genome Nomenclature Committee.

Comment on this Page
Privacy Statement  |   Copyright, Warranty & Disclaimer  |   Contact Us
Copyright © 2001-2011, T1DBase | Version 4.8 | PMID:20937630
Printed on Sun February 05, 2012