Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest

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Abstract

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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Figure 1: Mest targeting and derivation of Mest-deficient mice.
Figure 2: Growth retardation of Mest+/- mice.
Figure 3: Mest expression in the nervous system.
Figure 4: Reversible transcriptional silencing of the maternally inherited Mesttm1Lef allele.
Figure 5: Decreased reproductive fitness and abnormal maternal behaviour of Mest+/- females.

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Acknowledgements

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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Correspondence to M. Azim Surani.

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