Faculty Collaboration Database

Sequence variation and expression of the Gimap gene family in the BB rat. Exp Diabetes Res 2009;2009:835650

Date

05/08/2009

Pubmed ID

19421422

Pubmed Central ID

PMC2676327

DOI

10.1155/2009/835650

Scopus ID

2-s2.0-67650322087 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

Positional cloning of lymphopenia (lyp) in the BB rat revealed a frameshift mutation in Gimap5, 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 seven Gimap genes in the congenic DR.lyp rat line with 2 Mb of BB DP DNA introgressed onto the DR genetic background. All (100%) DR.(lyp/lyp) rats are lymphopenic and develop type 1 diabetes (T1D) by 84 days of age while DR.(+/+) rats remain T1D and lyp resistant. Among the seven Gimap genes, the Gimap5 frameshift mutation, a mutant allele that produces no protein, had the greatest impact on lymphopenia in the DR.(lyp/lyp) rat. Gimap4 and Gimap1 each had one amino acid substitution of unlikely significance for lymphopenia. Quantitative RT-PCR analysis showed a reduction in expression of all seven Gimap genes in DR.(lyp/lyp) spleen and mesenteric lymph nodes when compared to DR.(+/+). Only four; Gimap1, Gimap4, Gimap5, and Gimap9 were reduced in thymus. Our data substantiates the Gimap5 frameshift mutation as the primary defect with only limited contributions to lymphopenia from the remaining Gimap genes.

Author List

Rutledge EA, Fuller JM, Van Yserloo B, Moralejo DH, Ettinger RA, Gaur P, Hoehna JL, Peterson MR, Jensen R, Kwitek AE, Lernmark A

Author

Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Animals, Congenic
Base Sequence
Chromosome Mapping
Cloning, Molecular
DNA Primers
DNA, Complementary
Diabetes Mellitus, Type 1
Disease Models, Animal
Female
Frameshift Mutation
GTP-Binding Proteins
Gene Expression
Genetic Variation
Lymphoid Tissue
Lymphopenia
Male
Molecular Sequence Data
Multigene Family
RNA, Messenger
Rats
Rats, Inbred BB
Sequence Homology, Amino Acid
Tissue Distribution