We report the isolation, by RT‐PCR, of partial cDNAs encoding the rat peroxisome proliferator‐activated receptor (PPAR) isoforms PPARα, PPARβ, and PPARγ and the rat retinoid X receptor (RXR) isoforms RXRα, RXRβ, and RXRγ. These cDNAs were used to generate antisense RNA probes to permit analysis, by the highly sensitive and discriminatory RNase protection assay, of the corresponding mRNAs in rat brain regions during development. PPARα, PPARβ, RXRα, and RXRβ mRNAs are ubiquitously present in different brain regions during development, PPARγ mRNA is essentially undetectable, and RXRγ mRNA is principally localised to cortex. We demonstrate, for the first time, the presence of PPAR and RXR mRNAs in primary cultures of neonatal meningeal fibroblasts, cerebellar granule neurons (CGNs), and cortical and cerebellar astrocytes and in primary cultures of adult cortical astrocytes. PPARα, PPARβ, RXRα, and RXRβ mRNAs are present in all cell types, albeit that PPARα and RXRα mRNAs are at levels near the limit of detection in CGNs. PPARγ mRNA is expressed at low levels in most cell types but is present at levels similar to those of PPARα mRNA in adult astrocytes. RXRγ mRNA is present either at low levels, or below the level of detection of the assay, for all cell types studied.

. We present here the isolation of a cDNA for FMO3 of iiian. Thc sequcncc of this cDNA and the atnino acid sequcnce deduced from it differ substantially from those previously reported for this member of the FMO family of man. In addition, we have investigated, by quantitative KNase protection assays, the expression in several foetal and adult human tissues of genes encoding FMOl, FM03 and FM04. Our results demonstrate that, in the adult, FMOI is expressed in kidney hut not in livcr, whcrcas in the foetus it is expressed in both organs. The lack of expression of FA401 in adult hurnan liver is in marked contrast to the situation in other mammals, such as pig and rabbit, in which FMOl constitutvs ii major form of the enzyinc in the liver of the adult animal. The rnRNA encoding FMO3 is abundant in adult liver and i s also present, in low abundance, in some foetal tissues. Thus, FMOI and FMO3 are bnth subject to developmcntal and tissue-specific rcgulation, with a developnicntal switch in the expression of the genes taking place in the liver. FMO4 mRNA is present i n low abundancc in several foetal arid adult tissues and thus the corresponding gene appears to be expressed constitutively.Keyworcls: cDNA; sequence ; flavin-containing nionooxygcnases ; regulation: human.The microsomal flavin-containing rnonooxygenase (FMO) catalyscs the NADPH-dcpendent oxidativc tnetabolism of numerous foreign compounds including many therapeutic agents and pesticides (Ziegler, 1990(Ziegler, , 1993. FMO substrates are restricted to compounds that contain ii soft nucleophilic heteroatom as the sitc for oxygenation by the C4a-peroxyflavin fortn of the FAD prosthetic group. One such conipound is the simple dictary-derived aliphatic atnine trinicthylaminc. Oxidation of trimcthylamine to its N-oxide is mediated by FMO, and is subject to :I genetic polyinorphisrri in iniiii that results in 11 subpopulation with reduced trimethylainine N-oxidation capacity (A1 Waiz et al., 1987). Such individuals excrete relatively large amounts of triincthylatnine in thcir urine, sweat and breath, and exhibit a fishy body odour, characteristic of the associated disorder triinethylaminuria or fish-odour syndrome (Humbert et id., 1970; Shelley and Shelley, 19x4 The enzyrnic properties and catalytic riiechanisiii of FMO were c)riginally characterized using a hornogcneous protein prrparation froin pig liver (Ziegler and Mitchell, 1972). FMOs have subsequently been purified and characteriml from the livers of sevcral other species (Kiinura et al., 19x3; Sabourin ct al., 1084; Tynes aid Hodgson, 1985) und from rahbit and mouse lung (Williams et al., 1984; Tynes zt al., 1985). Observed diffexnccs in immunological cross-rcactivities, suhstrale prcfcrences and other physical properties between livcr and lung FMOs provided evidence for the existence of' multiplc forms of the enxymc (Williams et al., 1984; Tynes et al.. 1985Tynes et al.. , 1986; Poulsen ct d., 19x6). More reccntly, the isolation of cDNA clones that encode different forms of the enzyrne has confirnicd t...

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