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Molecular and Cellular Biology, October 2002, p. 7313-7324, Vol. 22, No. 20
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.20.7313-7324.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mouse Af9 Is a Controller of Embryo Patterning, Like Mll, Whose Human Homologue Fuses with AF9 after Chromosomal Translocation in Leukemia

Emma C. Collins, Alexandre Appert, Linda Ariza-McNaughton,{dagger} Richard Pannell, Yoshihiro Yamada,{ddagger} and Terence H. Rabbitts*

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

Received 14 May 2002/ Returned for modification 11 July 2002/ Accepted 17 July 2002

Chromosomal translocation t(9;11)(p22;q23) in acute myeloid leukemia fuses the MLL and AF9 genes. We have inactivated the murine homologue of AF9 to elucidate its normal role. No effect on hematopoiesis was observed in mice with a null mutation of Af9. However, an Af9 null mutation caused perinatal lethality, and homozygous mice exhibited anomalies of the axial skeleton. Both the cervical and thoracic regions were affected by anterior homeotic transformation. Strikingly, mice lacking functional Af9 exhibited a grossly deformed atlas and an extra cervical vertebra. To determine the molecular mediators of this phenotype, analysis of Hox gene expression by in situ hybridization showed that Af9 null embryos have posterior changes in Hoxd4 gene expression. We conclude that the Af9 gene is required for normal embryogenesis in mice by controlling pattern formation, apparently via control of Hox gene regulation. This is analogous to the role of Mll, the murine homolog of human MLL, to which the Af9 gene fuses in acute myeloid leukemias.


* Corresponding author. Mailing address: MRC Laboratory of Molecular Biology, Hills Rd., Cambridge CB2 2QH, United Kingdom. Phone: 01223-402286. Fax: 01223-412178. E-mail: thr{at}mrc-lmb.cam.ac.uk.

{dagger} Present address: CRUK, Lincolns Inn Fields, London WC2A 3PX, United Kingdom.

{ddagger} Present address: Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.


Molecular and Cellular Biology, October 2002, p. 7313-7324, Vol. 22, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.20.7313-7324.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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