Characterization of the two zebrafish orthologues of the KAL-1 gene underlying X chromosome-linked Kallmann syndrome

The gene underlying X chromosome-linked Kallmann syndrome, KAL-1, has been identified for several years, yet its role in development is still poorly u nderstood. In order to take advantage of the zebrafish as a model in develo pmental genetics, we isolated the two KAL-1 orthologues, kal1.1 and kal1.2, in this species. Comparison of deduced protein sequences with the human on e shows 75.5 and 66.5% overall homology, respectively. The most conserved d omains are the whey acidic protein-like domain and the first of four fibron ectin-like type III repeats. However, kal1.2 putative protein lacks the bas ic C-terminal domain (20 residues) found in kal1.1 and KAL-1. The expressio ns of kal1.1 and kal1.2 were studied in the embryo between 6 and 96 hours p ost fertilization using whole-mount in situ hybridization. Although a few s tructures express both genes, kal1.1 and kal1.2 expression patterns are lar gely non-overlapping. Taken together, these patterns match fairly well thos e previously reported for human KAL-1 and chicken kal1. As regards the olfa ctory system, kal1.1 is expressed, from 37 h.p.f. onward, in the presumptiv e olfactory bulbs, whereas kal1.2 transcript is only detected, from 48 h.p. f., in the epithelium of the nasal cavity. The relevance of the zebrafish a s an animal model for studying both the function of KAL-1 in normal develop ment and the developmental failure leading to the olfactory defect in Kallm ann syndrome, is discussed. (C) 2000 Elsevier Science Ireland Ltd. All righ ts reserved.