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Molecular and Cellular Biology, March 2004, p. 2063-2073, Vol. 24, No. 5
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.5.2063-2073.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Null Mutation of the Lmo4 Gene or a Combined Null Mutation of the Lmo1/Lmo3 Genes Causes Perinatal Lethality, and Lmo4 Controls Neural Tube Development in Mice

E. Tse ,^, A. J. H. Smith,^, S. Hunt,^|| I. Lavenir, A. Forster, A. J. Warren, G. Grutz,^¶ L. Foroni,^# M. B. L. Carlton, W. H. Colledge, T. Boehm, and T. H. Rabbitts^*

MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom

Received 30 September 2003/ Accepted 9 November 2003

The LIM-only family of proteins comprises four members; two of these (LMO1 and LMO2) are involved in human T-cell leukemia via chromosomal translocations, and LMO2 is a master regulator of hematopoiesis. We have carried out gene targeting of the other members of the LIM-only family, viz., genes Lmo1, Lmo3 and Lmo4, to investigate their role in mouse development. None of these genes has an obligatory role in lymphopoiesis. In addition, while null mutations of Lmo1 or Lmo3 have no discernible phenotype, null mutation of Lmo4 alone causes perinatal lethality due to a severe neural tube defect which occurs in the form of anencephaly or exencephaly. Since the Lmo1 and Lmo3 gene sequences are highly related and have partly overlapping expression domains, we assessed the effect of compound Lmo1/Lmo3 null mutations. Although no anatomical defects were apparent in compound null pups, these animals also die within 24 h of birth, suggesting that a compensation between the related Lmo1 and 3 proteins can occur during embryogenesis to negate the individual loss of these genes. Our results complete the gene targeting of the LIM-only family in mice and suggest that all four members of this family are important in regulators of distinct developmental pathways.

E.T. and A.J.H.S. made equal contributions.

Present address: Division of Haematology and Oncology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.

Present address: Centre for Genome Research, University of Edinburgh, Edinburgh EH9 3JQ, United Kingdom.

^¶ Present address: Institute for Medical Immunology, Medical School Charité, D-10117 Berlin, Germany.

^|| Present address: Department of Anatomy and Developmental Biology, University College, London WC1E 6BT, United Kingdom.

^# Present address: Department of Haematology, Royal Free Hospital, London NW3 2QG, United Kingdom.

Present address: CRC-Wellcome Institute, Cambridge CB2 3EG, United Kingdom.

Present address: Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, United Kingdom.

Present address: Department of Developmental Immunology, Max-Planck-Institut für Immunbiologie, Freiburg D-79108, Germany.

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