Combining In Vivo and In Vitro Approaches To Identify Human Odorant Receptors Responsive to Food Odorants

Olfactory perception plays an important role in food flavor. Humans have around 400 odorant receptors (ORs), which can be activated by an enormous number of odorants in a combinatorial fashion. To date, only a few odorant receptors have been linked to their respective odorants, due to the difficulties in expressing these receptor proteins in heterologous cell systems. In vivo approaches allow for the analysis of odorant-receptor interactions in their native environment and have the advantage that the complete OR repertoire is simultaneously tested. Once mouse odorant receptor pairs are defined, one can search for the corresponding human orthologues, which can be validated against the odorants in heterologous cells. Thus, the combination of in vivo and in vitro methods should contribute to the identification of human ORs that recognize odorants of interest, such as key food odorants.Fundacao de Amparo a Pesquisa do Estado de Sao PauloConselho Nacional de Desenvolvimento Cientifico e TecnologicoCoordenacao de Aperfeicoamento de Pessoal de Nivel SuperiorUniv Fed Sao Paulo, Dept Biol Sci, Diadema Campus, Sao Paulo, BrazilUniv Sao Paulo, Dept Biochem, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biol Sci, Diadema Campus, Sao Paulo, BrazilWeb of Scienc

Mutations in collagen 18A1 (COL18A1) and their relevance to the human phenotype

Collagen XVIII, a proteoglycan, is a component of basement membranes (BMs). There are three distinct isoforms that differ only by their N-terminal, but with a specific pattern of tissue and developmental expression. Cleavage of its C-terminal produces endostatin, an inhibitor of angiogenesis. In its N-terminal, there is a frizzled motif which seems to be involved in Wnt signaling. Mutations in this gene cause Knobloch syndrome KS), an autosomal recessive disorder characterized by vitreoretinal and macular degeneration and occipital encephalocele. This review discusses the effect of both rare and polymorphic alleles in the human phenotype, showing that deficiency of one of the collagen XVIII isoforms is sufficient to cause KS and that null alleles causing deficiency of all collagen XVIII isoforms are associated with a more severe ocular defect. This review besides illustrating the functional importance of collagen XVIII in eye development and its structure maintenance throughout life, it also shows its role in other tissues and organs, such as nervous system and kidney