A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian development

Breckenridge, R. A., Kelly, P., Nandi, M., Vallance, P. J., Ohun, T. J. and Leiper, J. (2010) A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian development. International Journal of Developmental Biology, 54(1), pp. 215-226. (doi:10.1387/ijdb.072356rb) (PMID:19757398)

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Abstract

Nitric oxide has been linked to a number of embryonic processes, yet the role of nitric oxide signalling in development remains largely unknown. Dimethylarginine Dimethylaminohydrolase 1 and 2 (DDAH1/2) catalyse the breakdown of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide production, and may also have nitric oxide-independent functions. We have generated transgenic mice targeting the DDAH1 and DDAH2 loci. Here we report that homozygous DDAH1 null embryos are generated at low frequency, and do not progress through embryonic development. During normal development DDAH1 RNA is expressed in the left ventricle, cardiac outflow tract and developing vasculature. In contrast, DDAH2 homozygous null mice are viable and fertile, with a normal lifespan. DDAH2 expression is seen in the developing left ventricle and cardiac outflow tract, and additionally in the peripheral nervous system. Both DDAH1 and 2 are expressed in the developing limb buds in patterns overlapping areas with high nitric oxide synthase activity. These expression patterns implicate DDAH1 and DDAH2 in embryonic development, possibly through specific effects on nitric oxide pathways.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leiper, Professor James
Authors: Breckenridge, R. A., Kelly, P., Nandi, M., Vallance, P. J., Ohun, T. J., and Leiper, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:International Journal of Developmental Biology
Publisher:University of the Basque Country Press
ISSN:0214-6282
ISSN (Online):1696-3547
Published Online:11 September 2009

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