Impairment in motor learning of somatostatin null mutant mice

Somatostatin was first identified as a hypothalamic factor which inhibits t he release of growth hormone from the anterior pituitary (somatotropin rele ase inhibitory factor, SRIF). Both SRIF and its receptors were subsequently found widely distributed within and outside the nervous system. in the adu lt as well as in the developing organism. Reflecting this wide distribution . somatostatin has: been implicated regulating a diverse array of biologica l processes. These include body growth, homeostasis, sensory perception. au tonomous functions, rate of intestinal absorption, behavior, including cogn ition and memory, and developmental processes. We produced null mutant mice lacking somatostatin through targeted mutagenesis. The mutant mice are hea lthy, fertile, and superficially indistinguishable from their heterozygous and wildtype littermates. A 'first round' phenotype screen revealed that mi ce lacking somatostatin have elevated plasma growth hormone levels, despite normal body size, and have elevated basal plasma corticosterone levels. In order to uncover subtle and unexpected differences, we carried out a syste matic behavioral phenotype screen which identified a significant impairment in motor learning revealed when increased demands were made on motor coord ination. Motor coordination and motor learning require an intact cerebellum . While somatostatin is virtually absent from the adult cerebellum, the lig and and its receptor(s) are transiently expressed at high levels in the dev eloping cerebellum This result suggests the functional significance of tran sient expression of SRIF and its receptors in the development of the cerebe llum. (C) 2001 Elsevier Science B.V. All rights reserved.