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Operant Sensation Seeking in the Mouse
Published on: November 10, 2010
Several classical mouse inbred strains, including DBA/2, NOD/Lt, FVB/N, and SJL/J, carry a putative loss-of-function
Carlos J Perez1, Aline Dumas, Luc Vallières
1e Department of Molecular Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Smithville, TX, USA.
Abstract:
G protein-coupled receptor 84 (GPR84) is a 7-transmembrane protein expressed on myeloid cells that can bind to medium-chain free fatty acids in vitro. Here, we report the discovery of a 2-bp frameshift deletion in the second exon of the Gpr84 gene in several classical mouse inbred strains. This deletion generates a premature stop codon predicted to result in a truncated protein lacking the transmembrane domains 4-7. We sequenced Gpr84 exon 2 from 58 strains representing different groups in the mouse family tree and found that 14 strains are homozygous for the deletion. Some of these strains are DBA/1J, DBA/2J, FVB/NJ, LG/J, MRL/MpJ, NOD/LtJ, and SJL/J. However, the deletion was not found in any of the wild-derived inbred strains analyzed. Haplotype analysis suggested that the deletion originates from a unique mutation event that occurred more than 100 years ago, preceding the development of the first inbred strain (DBA), from a Mus musculus domesticus source. As GPR84 ostensibly plays a role in the biology of myeloid cells, it could be relevant 1) to consider the existence of this Gpr84 nonsense mutation in several mouse strains when choosing a mouse model to study immune processes and 2) to consider reevaluating data obtained using such strains.
Insights
A common G protein-coupled receptor 84 (GPR84) gene deletion in mice creates a non-functional protein. This finding impacts research using these mouse models, particularly in immunology.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- G protein-coupled receptor 84 (GPR84) is a transmembrane protein found on myeloid cells.
- GPR84 binds to medium-chain free fatty acids.
- Its role in myeloid cell biology is significant for immune processes.
Purpose of the Study:
- To report the discovery of a specific genetic deletion in the Gpr84 gene in common mouse strains.
- To investigate the prevalence and origin of this Gpr84 mutation.
- To highlight the implications for using these mouse strains in research.
Main Methods:
- Sequencing of the Gpr84 gene's second exon across 58 mouse strains.
- Haplotype analysis to trace the mutation's origin.
- Identification of strains carrying the deletion.
Main Results:
- A 2-base pair frameshift deletion was identified in the Gpr84 gene's second exon.
- This deletion results in a premature stop codon, leading to a truncated, non-functional GPR84 protein.
- Fourteen of 58 analyzed mouse strains are homozygous for this deletion, including DBA/1J, DBA/2J, FVB/NJ, LG/J, MRL/MpJ, NOD/LtJ, and SJL/J.
- The deletion was absent in wild-derived inbred strains.
- Haplotype analysis suggests the mutation occurred over 100 years ago from a Mus musculus domesticus source.
Conclusions:
- The Gpr84 gene harbors a nonsense mutation in several classical mouse inbred strains.
- Researchers should consider this Gpr84 mutation when selecting mouse models for studying immune responses.
- Existing data from studies using these mouse strains may need reevaluation due to the non-functional GPR84 protein.
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