Cloning and characterization of a new type of mouse chemokine

We report here the identification and characterization of the mouse homologue of a human CX₃C chemokine described by F. Bazan et al. (1997, Nature 385, 640-644). Termed fractalkine, this molecule constitutes a fourth or chemokine structural type that displays a novel CX₃C sequence fingerprint. Distinct from the α, β, or γ chemokine families, the polypeptide chain of CX₃C predicts a 373-amino-acid type I transmembrane glycoprotein with the chemokine domain resting on top of an extended mucin- like stalk. Comparison of the mouse and human protein chains shows a high degree of conservation in all the globular segments with the exception of the stalk portion. The striking identity of an amino acid stretch encompassing a putative juxtamembrane cleavage site suggests the evolutionary conservation of both membrane-bound and processed CX₃C forms. Northern analysis reveals the presence of mouse CX₃C mRNA in heart, brain, lung, kidney, skeletal muscle, and testis tissues. The mouse CX₃C gene was further localized to the central region of chromosome 8 by interspecific backcross mapping; a related locus was detected on chromosome 11. The novel location of this gene from other chemokine gene clusters adds to the notion that CX₃C is a fundamentally new class of chemokine.