Abstract: The invention features a method of screening for an agent that inhibits intracellular phosphodiesterase 10A activity, comprising administering an agent to striatal medium spiny neurons and submaximally activating adenylate cyclase, administering an agent to striatal medium spiny neurons and submaximally activating guanylate cyclase, measuring cAMP generation and cGMP generation in the cells, and calculating the cAMP EC200 and the cGMP EC200, wherein the agent is identified as a PDE10A inhibitor if the ratio of cAMP EC200/cGMP EC200 is comparable to the ratio produced by administration of papaverine under the same assay conditions. Also featured are rat PDE10A polynucleotide and polypeptide sequences.

Abstract: The invention features non-human mammals and animal cells that contain a targeted disruption of a phosphodiesterase 10A (PDE10A) gene.

Abstract: The invention features a method of screening for an agent that inhibits intracellular phosphodiesterase 10A activity, comprising administering an agent to striatal medium spiny neurons and submaximally activating adenylate cyclase, administering an agent to striatal medium spiny neurons and submaximally activating guanylate cyclase, measuring cAMP generation and cGMP generation in the cells, and calculating the cAMP EC200 and the cGMP EC200, wherein the agent is identified as a PDE10A inhibitor if the ratio of cAMP EC200/cGMP EC200 is comparable to the ratio produced by administration of papaverine under the same assay conditions. Also featured are rat PDE10A polynucleotide and polypeptide sequences.

Abstract: This invention relates to modified Yarrowia lipolytica LEU2 gene promoters; modified Y. lipolytica LEU2 genes comprising such modified Y. lipolytica LEU2 gene promoters; and vectors comprising such modified Y. lipolytica LEU2 genes. This invention also relates to vectors comprising a Y. lipolytica DNA sequence LEU2 genes. This invention also relates to vectors comprising a Y. lipolytica DNA sequence sufficient for integrative transformation of Y. lipolytica; vectors which comprise a nucleotide sequence coding for a polypeptide and a promoter functional in Y. lipolytica operably linked thereto; E. coli transformants which comprise vectors according to this invention; Y. lipolytica transormants which comprise an expression vector according to this invention; methods of producing Y. lipolytica transformants comprising multiple integrated expression vectors; strains of Y. lipolytica useful in the preparation of such transformants; methods of producing polypeptides with certain of the Y.