Kallmann syndrome is
hypogonadotropic hypogonadism coupled with
anosmia. A morphological study found that the endocrine disorder in X-linked
Kallmann syndrome is due to failed migration of
gonadotropin releasing-hormone (
GnRH) neurons from the olfactory placode to the brain during development.
Anosmia results from agenesis of the olfactory bulbs and tracts. The gene responsible for the X-linked form of
Kallmann syndrome, KAL-1, has been characterized. The orthologues of KAL-1 have been isolated in the chick and the zebrafish, but still await identification in rodents. In the present study, we used polyclonal and
monoclonal antibodies to the human KAL-1 encoded
protein, anosmin-1, in a primitive mammal, the Asian
musk shrew.
Musk shrews are insectivores and are therefore evolutionarily closer to primates than rodents. By immunoblot analysis of
musk shrew tissues, a band of the expected apparent molecular mass (95 kDa) was detected in several structures of the central nervous system, but not in liver or muscle, which is consistent with the gene expression pattern previously reported in the chick. By immunohistochemical analysis, anosmin-1 was detected in the developing olfactory epithelium, the olfactory, vomeronasal and terminalis nerves, the olfactory bulbs, the cerebellum and the cerebral cortex and in several other regions of the brain, during
musk shrew embryogenesis. Furthermore, migrating
gonadotropin releasing-hormone (
GnRH)-immunoreactive neurons were seen in close association with anosmin-1-immunoreactive fibers. Assuming that the
protein is present at the surface of these fibers, we suggest a possible direct role of anosmin-1 in the migration of
GnRH neurons in this species.