Mest (also known as Peg1), an imprinted gene expressed only from the paternal allele during development, was disrupted by gene targeting in embryonic stem (ES) cells. The targeted mutation is imprinted and reversibly silenced by passage through the female germ line. Paternal transmission activates the targeted allele and causes embryonic growth retardation associated with reduced postnatal survival rates in mutant progeny. More significantly, Mest-deficient females show abnormal maternal behaviour and impaired placentophagia, a distinctive mammalian behaviour. Our results provide evidence for the involvement of an imprinted gene in the control of adult behaviour.
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We thank the members of our group for their help, especially J. Ainscough and R. John for their valuable comments on this work, J. Dixon for the IRES-βgeo construct pIFS and A. Nagy for the R1 ES cells. This work was supported by a grant from the Wellcome Trust to M.A.S. L.L. was a Research Fellow of the National Cancer Institute of Canada, supported with funds provided by the Terry Fox Run, and S.V. was supported by a Fellowship from EMBO.
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