A cDNA clone homologous with the human neuropeptide Y (NPY)-Y5 receptor has been isolated from a mouse brain cDNA library. Analysis of the predicted amino acid sequence indicates that the polypeptide encoded by this cDNA is 89% and 97% identical to the human and rat NPY-YS receptors, respectively, but has a repeat sequence of 21-amino acid residues, unlike the human and rat NPY-YS receptors, in its N-terminal region. Northern blot analysis indicated that the mouse NPY-YS receptor mRNA was highly expressed in the brain, but not in the heart, kidney, spleen, lung, liver, skeletal muscle, and testis. A genomic DNA clone encoding the mouse NPY-YS receptor has also been cloned and used as a probe for fluorescence in situ hybridization analysis. The mouse NPY-YS receptor gene consists of at least two exons with a 7.0 kbp-long intronic sequence and is localized in the chromosome 8B3-C2 region. Restriction mapping, partial sequencing, and hybridization analysis of the mouse NPY-YS and NPY-Y1 receptor genes were used to determine the relationship between the two genes in the chromosome 8B3-C2 region. The mouse NPY-YS receptor gene can map about 10 kbp upstream of the transcriptional initiation sites of the NPY-Y1 receptor gene with an opposite orientation. (C) 1997 Elsevier Science B.V.