Determination of the Expression Pattern and the Phenotype of Knockout Mice of Orphan 7TM Proteins

Determination of the expression pattern of 7TM proteins may provide useful information for ligand-receptor pairing as exemplified by GPR109B, the receptor for nicotinic acid receptor [31]. GPR109B was deorphanized on the basis of its restricted expression pattern in adipose tissue and spleen, two main tissues of nicotinic acid action (Fig. 7.1). The generation of knockout animals is increasingly employed to elucidate the biological function of orphan 7TM proteins [32-34]) (Table 7.2 ; Fig. 7.1). For example, expression of the orphan Mas-related gene (Mrg) E receptor in the nervous system and the phenotype of mice lacking MrgE receptors revealed its involvement in pain [35]. Recently, a comparative study of GPR85 overexpressing transgenic mice and GPR85 knockout mice showed a role of GPR85 in the control of the brain size and in the pathophysiology of psychiatric disorders [36]. These functional studies constitute a first step toward the deorphanization of 7TM proteins.

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