PHENOTYPIC EXPRESSION OF AN OXYTOCIN PEPTIDE NULL MUTATION IN MICE

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Homologous recombination techniques were used to produce mice with an oxytocin gene deletion. Radiommunoassay immunohistochemical staining, and in situ hybridization confirmed that oxytocin is not expressed in these mice and that intermediate levels of oxytocin are expressed in mice heterozygous for the oxytocin deletion. Oxytocin knock-out mice mate, give birth, and express normal maternal behavior, however milk ejection is disrupted. AVP gene expression was not increased in OT knockout mice, nor were there changes in OT receptors. Chronic treatment with an OT antagonist given ICV also did not alter maternal behavior in knockout mice. The lack of effects on sexual and maternal behaviors may be related to strain and species differences in underlying neural mechanisms. The objective of this project is to generate a comprehensive behavioral phenotype of the OT knockout mouse. Examination of other aspects of social and cognitive behavior are on-going in these animals. P reliminary findings include a decreased rate of pup ultrasonic calls and an increase in aggression in the homozygous knockout mice. These analyses include comparisons of the chimeric knockout and wild-type mice with the C57BL/6J and 129/J background strains in an effort to control for potential background contamination. Additional studies examine the influence of parental genotype on the behavioral development of offspring with the null mutation. Initial findings suggest that parental factors may "rescue" some behavioral deficits. These studies demonstrate the complex interaction of genetic background, parental influence and developmental compensation in the ultimate behavioral expression of a mutational phenotype.