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Molecular and Cellular Biology, August 2001, p. 5658-5666, Vol. 21, No. 16
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.16.5658-5666.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Gene Targeting Reveals a Crucial Role for MTG8 in the Gut

Franco Calabi,1,* Richard Pannell,2 and Gordana Pavloska1

Institute of Child Health, London WCIN 1EH,1 and MRC Laboratory of Molecular Biology, Cambridge CB2 2QH,2 United Kingdom

Received 7 February 2001/Returned for modification 2 April 2001/Accepted 23 May 2001

The MTG8 (ETO) locus is involved in a reciprocal exchange with runx1 in the t(8;21) of acute myeloid leukemia. It is a member of a small gene family encoding transcriptional regulators that interact with corepressors and histone deacetylase. However, the physiologic cellular processes controlled by MTG8 are not known. In order to gain an insight into the latter, we have generated mutant mice with an insertional inactivation at the locus, which disrupts transcription of exon 2. The postnatal viability of homozygous mutants was greatly reduced. In approximately 25% the midgut was missing, whereas practically all pups surviving past the first 2 days showed severe growth impairment, which was likely due to a gross disruption of the gut architecture. The latter phenotype could be traced back to late embryonic development. No difference in gut cell differentiation or proliferation was found compared to wild-type littermates. Levels of factors known to be involved in gut morphogenesis were also unchanged. MTG8 is expressed in the outermost layers of the developing gut from at least E9.5. Thus, MTG8 plays a novel, essential role in the gastrointestinal system.

* Corresponding author. Mailing address: Developmental Biology Unit, The Institute of Child Health, 30 Guilford St., London WCIN 1EH, United Kingdom. Phone: 44-20-7813-8492. Fax: 44-20-7831-4366. E-mail: fcalabi{at}hgmp.mrc.ac.uk.

Molecular and Cellular Biology, August 2001, p. 5658-5666, Vol. 21, No. 16
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.16.5658-5666.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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