title: A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian development.
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.
authors.affiliation: Centre for Clinical Pharmacology, University College London, BHF Laboratories, London, UK. rbrecke@nimr.mrc.ac.uk
authors.forename: Ross A
authors.initials: RA
authors.lastname: Breckenridge
authors.forename: Peter
authors.initials: P
authors.lastname: Kelly
authors.forename: Manasi
authors.initials: M
authors.lastname: Nandi
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Vallance
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ohun
authors.forename: James
authors.initials: J
authors.lastname: Leiper
mesh_terms: D000581:Amidohydrolases / Q000502:physiology*; D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology* / Q000201:enzymology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism; D015347:RNA Probes
chemical_list: D015347:RNA Probes; D009569:Nitric Oxide; D000581:Amidohydrolases; C059999:dimethylargininase