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Congenital cystic adenomatoid malformation (CCAM) is a developmental lung abnormality characterized by abnormal proliferation of mesenchymal elements and failure of bronchiolar structures to mature, ultimately resulting in the compression of normal pulmonary tissue and mediastinal shift with rapid expansion of cysts. Although various clinical and pathologic studies of CCAM in humans exist, CCAM has yet to be reported in animals, even in nonhuman primates. In the present study, histopathologic analyses of a neonatal cynomolgus monkey that died 17 days after birth revealed that normal lung architecture was replaced by disorganized overgrowths of cysts lined with simple cuboidal epithelium. The epithelium projected a few ciliates into the air spaces and produced mucus. To our knowledge, this is the first case study describing CCAM or a CCAM-like lesion in nonhuman primates.

Retinoid X receptors (RXRs), along with retinoic acid (RA) receptors (RARs), mediate the effects of RA on gene expression. Three subtypes of RXRs (alpha, beta, and gamma) which bind to and are activated by the 9-cis stereoisomer of RA have been characterized. They activate gene transcription by binding to specific sites on DNA as homodimers or as heterodimers with RARs and other related nuclear receptors, including the vitamin D receptor, thyroid hormone receptors (TRs), and peroxisome proliferator-activated receptors. Two additional RXR subtypes (delta and epsilon) isolated from zebra fish cDNA libraries are described here; although both subtypes form DNA-binding heterodimers with RARs and TR, neither binds 9-cis RA, and both are transcriptionally inactive on RXR response elements. In cotransfection studies with TR, the delta subtype was found to function in a dominant negative manner, while the epsilon subtype had a slight stimulatory effect on thyroid hormone (T3)-dependent transcriptional activity. The discovery of these two novel receptors in zebra fish expands the functional repertoire of RXRs to include ligand-independent and dominant negative modulation of type II receptor function.

The striped pattern of fushi tarazu (ftz) expression found in the blastoderm of the Drosophila melanogaster embryo is generated largely through complex interactions between multiple transcription factors that bind to the zebra element of the ftz gene. A motif in the zebra element, the FTZ-F1 recognition element (F1RE), has been shown to bind a transcription factor, FTZ-F1 alpha, that is a member of the nuclear receptor family. We recently identified a second, related member of this family, FTZ-F1 beta, that also binds to this motif. To investigate the possibility that FTZ-F1 alpha and FTZ-F1 beta coregulate ftz transcription through the F1RE, we have studied the DNA binding properties of FTZ-F1 alpha and FTZ-F1 beta. We demonstrate that recombinant FTZ-F1 alpha and FTZ-F1 beta proteins produce similar in vitro DNase I footprint patterns on a 14-nucleotide region of the zebra element and bind to this site with similar affinities and sequence specificities. Using wild-type and N-terminally truncated receptors, we have determined that FTZ-F1 alpha and FTZ-F1 beta both bind as monomers to the 9-bp F1RE in the zebra element, as well as to an imperfect inverted F1RE repeat present in the Drosophila alcohol dehydrogenase gene. A polyclonal antibody raised against FTZ-F1 beta identifies a predominant F1RE-binding component in embryonic nuclear extracts. Although FTZ-F1 alpha is also present in these extracts, FTZ-F1 alpha and FTZ-F1 beta do not appear to form heterodimers with each other. Cotransfection assays in mammalian cell culture indicate that both receptors contribute to the net transcriptional activity of a reporter gene through their direct interaction with the F1RE. These data suggest that FTZ-F1 alpha and FTZ-F1 beta likely coregulate common target genes by competition for binding to a 9-bp recognition element.