New rat brain gamma-hydroxybutyrate receptor and its encoding nucleic acid, useful for identifying agents for treating e.g. epilepsy

摘要

A purified isolated or recombinant polypeptide (I) comprising: (a) a 512 amino acid (aa) sequence (S1) fully defined in the specification; (b) a fragment of (S1) containing at least 5 aa; or (c) a homolog or variant of (S1) excluding the human tetraspan NET-4 (GenBank AAC 17120), is new. Independent claims are also included for the following: (1) a purified or isolated nucleic acid (II) encoding (I) (excluding GenBank sequences AA615405, AA967250 or AI467230); (2) a purified or isolated nucleic acid (IIa) containing at least 15 consecutive nucleotides of a 1567 base pair (bp) sequence (S2) fully defined in the specification or its complement or the corresponding RNA; (3) a nucleic acid identified by screening cDNA or genomic DNA libraries with (II) or (IIa); (4) a polypeptide (Ia) encoded by (IIa); (5) a cloning and/or expression vector (III) containing (II) or (IIa); (6) a host cell (IV) transformed with (III); (7) a non-human mammal that includes (IV); (8) a non-human mammal in which the nucleic acid sequence encoding the psi -hydroxybutyrate receptor (GHBR), i.e. (II) or (IIa), is non-functional or inactivated; (9) recombinant production of (I) by culturing (IV); (10) mono- or poly-clonal antibodies (Ab), or their fragments, chimeras and immunoconjugates, that selectively recognize (I); (11) screening (M1) for compounds (A) that interact with GHBR or with (II); (12) (A) identified this way; and (13) agents (A') that modulate expression or activity of GHBR.