Neuropeptide Y Y5 Receptor Knock-out mice

Introduction Neuropeptide Y (NPY), a 36-amino-acid neuromodulator abundantly expressed in the brain, has been implicated in the regulation of food intake and body weight. Pharmacological data suggest that NPY's stimulatory effect on appetite is transduced by the G-proteincoupled NPY Y5 receptor (Y5R). Technology description Younger Y5R-null mice feed and grow normally; however, they develop mild late-onset obesity characterized by increased body weight, food intake and adiposity. Fasting-induced refeeding is unchanged in younger Y5R-null mice and they exhibit normal sensitivity to leptin. Their response to intracerebroventricular (i.c.v.) administration of NPY and related peptides is either reduced or absent. The Y5R gene was disrupted in embryonic stem cells by homologous recombination using a targeting vector in which 760 bp of the Y5R coding region, including the translation initiation codon and the first five transmembrane spanning domains, were replace with the lacZ reporter gene and a neomycin resistant cassette. Correct targeting resulted in the insertion of the lacZ gene 94 bp 5’ of the Y5R translation initiation codon, which should place it under the control of the Y5R gene promoter. Related Publication(s)
Nat Med. 1998 Jun;4(6):718-21

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