title: Several classical mouse inbred strains, including DBA/2, NOD/Lt, FVB/N, and SJL/J, carry a putative loss-of-function allele of Gpr84.
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.
authors.affiliation: e Department of Molecular Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Smithville, TX, USA.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Perez
authors.forename: Aline
authors.initials: A
authors.lastname: Dumas
authors.forename: Luc
authors.initials: L
authors.lastname: Vallières
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guénet
authors.forename: Fernando
authors.initials: F
authors.lastname: Benavides
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D018389:Codon, Nonsense / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010802:Phylogeny; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion; D013045:Species Specificity
chemical_list: D018389:Codon, Nonsense; C507114:Gpr84 protein, mouse; D043562:Receptors, G-Protein-Coupled
keywords: G protein–coupled receptors; inbred mice; mouse models; spontaneous mutations