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Current Genomics


ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Invertebrate Models of Kallmann Syndrome: Molecular Pathogenesis and New Disease Genes

Author(s): Elia Di Schiavi and Davide Andrenacci

Volume 14, Issue 1, 2013

Page: [2 - 10] Pages: 9

DOI: 10.2174/1389202911314010002

open access plus


Kallmann Syndrome is a heritable disorder characterized by congenital anosmia, hypogonadotropic hypogonadism and, less frequently, by other symptoms. The X-linked form of this syndrome is caused by mutations affecting the KAL1 gene that codes for the extracellular protein anosmin-1. Investigation of KAL1 function in mice has been hampered by the fact that the murine ortholog has not been identified. Thus studies performed in other animal models have contributed significantly to an understanding of the function of KAL1. In this review, the main results obtained using the two invertebrate models, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster, are illustrated and the contribution provided by them to the elucidation of the molecular pathogenesis of Kallmann Syndrome is discussed in detail. Structure-function dissection studies performed in these two animal models have shown how the different domains of anosmin-1 carry out specific functions, also suggesting a novel intramolecular regulation mechanism among the different domains of the protein. The model that emerges is one in which anosmin-1 plays different roles in different tissues, interacting with different components of the extracellular matrix. We also describe how the genetic approach in C. elegans has allowed the discovery of the genes involved in KAL1-heparan sulfate proteoglycans interactions and the identification of HS6ST1 as a new disease gene.

Keywords: CeKal-1, DmKal-1, Morphogenesis, Axon branching, Animal models, Extracellular matrix, Pathogenesis, Caenorhabditis elegans, sulfate proteoglycans interactions, Drosophila melanogaster.

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