Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX-CKR.

We report here the identification and characterization of murine CCX-CKR, a high affinity receptor for the murine beta-chemokines SLC/mCCL21, MIP-3beta/mCCL19 and TECK/mCCL25. Unlike most other chemokine receptors, CCX-CKR is unable to mediate Ca(2+) fluxes upon ligand binding when expressed in HEK293 cells. Murine CCX-CKR is expressed predominantly in the heart and lung, but is detectable in most organs using RT-PCR. Interestingly, in brain and testis, an alternative mRNA form of CCX-CKR exists with a unique 5' untranslated region (5'UTR) that overlaps with a novel acyl-CoA dehydrogenase (ACD) gene. Analysis of human CCX-CKR shows that the expression profiles and alternative 5'UTR are conserved. However, in man, there are two copies of the CCX-CKR gene, one on chromosome 3 nestled within the ACD homologue, and one on chromosome 6. These genes encode proteins with only one amino acid difference, and their expression is independently regulated. This study identifies murine CCX-CKR, reveals complex regulation of CCX-CKR gene expression in mouse and man, and is suggestive of non-leukocytic targets for MIP-3beta/CCL19, SLC/CCL21 and TECK/CCL25.