The zebrafish as a model system for analyzing mammalian and native -crystallin promoter function.

Previous studies have used the zebrafish to investigate the biology of lens crystallin proteins and their roles in development and disease. However, little is known about zebrafish α-crystallin promoter function, how it compares to that of mammals, or whether mammalian α-crystallin promoter activity can be assessed using zebrafish embryos. We injected a variety of α-crystallin promoter fragments from each species combined with the coding sequence for green fluorescent protein (GFP) into zebrafish zygotes to determine the resulting spatiotemporal expression patterns in the developing embryo.

Loss of the small heat shock protein αA-crystallin does not lead to detectable defects in early zebrafish lens development.

Alpha crystallins are small heat shock proteins essential to normal ocular lens function. They also help maintain homeostasis in many non-ocular vertebrate tissues and their expression levels change in multiple diseases of the nervous and cardiovascular system and during cancer. The specific roles that α-crystallins may play in eye development are unclear.

Homeostatic generation of reactive oxygen species protects the zebrafish liver from steatosis.

Unlabelled: Nonalcoholic fatty liver disease is the most common liver disease in both adults and children. The earliest stage of this disease is hepatic steatosis, in which triglycerides are deposited as cytoplasmic lipid droplets in hepatocytes. Through a forward genetic approach in zebrafish, we found that guanosine monophosphate (GMP) synthetase mutant larvae develop hepatic steatosis.

Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm.

Period determination in the mammalian circadian clock involves the turnover rate of the repressors CRY and PER. We show that CRY ubiquitination engages two competing E3 ligase complexes that either lengthen or shorten circadian period in mice. Cloning of a short-period circadian mutant, Past-time, revealed a glycine to glutamate missense mutation in Fbxl21, an F-box protein gene that is a paralog of Fbxl3 that targets the CRY proteins for degradation.

Alzheimer disease: a tale of two prions.

Alzheimer disease (AD) has traditionally been thought to involve the misfolding and aggregation of two different factors that contribute in parallel to pathogenesis: amyloid-β (Aβ) peptides, which represent proteolytic fragments of the transmembrane amyloid precursor protein, and tau, which normally functions as a neuronally enriched, microtubule-associated protein that predominantly accumulates in axons. Recent evidence has challenged this model, however, by revealing numerous functional interactions between Aβ and tau in the context of pathogenic mechanisms for AD. Moreover, the propagation of toxic, misfolded Aβ and tau bears a striking resemblance to the propagation of toxic, misfolded forms of the canonical prion protein, PrP, and misfolded Aβ has been shown to induce tau misfolding in vitro through direct, intermolecular interaction.

Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β.

Extracellular plaques of amyloid-β and intraneuronal neurofibrillary tangles made from tau are the histopathological signatures of Alzheimer's disease. Plaques comprise amyloid-β fibrils that assemble from monomeric and oligomeric intermediates, and are prognostic indicators of Alzheimer's disease. Despite the importance of plaques to Alzheimer's disease, oligomers are considered to be the principal toxic forms of amyloid-β.

Mutation of zebrafish Snapc4 is associated with loss of the intrahepatic biliary network.

Biliary epithelial cells line the intrahepatic biliary network, a complex three-dimensional network of conduits. The loss of differentiated biliary epithelial cells is the primary cause of many congenital liver diseases. We identified a zebrafish snapc4 (small nuclear RNA-activating complex polypeptide 4) mutant in which biliary epithelial cells initially differentiate but subsequently disappear.

Significant association of glutamate receptor, ionotropic N-methyl-D-aspartate 3A (GRIN3A), with nicotine dependence in European- and African-American smokers.

The glutamate receptor gene, ionotropic N-methyl-D-aspartate 3A (GRIN3A), is one of the seven that code for subunits of N-methyl-D-aspartate receptors, which play an essential role at many synapses in the brain, regulating ion flow across membranes in response to glutamate signaling. In this study, we analyzed 25 single nucleotide polymorphisms (SNPs) within GRIN3A for association with nicotine dependence (ND), which was assessed by smoking quantity, heaviness of smoking index, and the Fagerström test for ND. Both individual SNP and haplotype association tests were performed in African-American (AA) and European-American (EA) samples as well as in the pooled sample consisting of 2,037 individuals from 602 nuclear families.

Significant association of the neurexin-1 gene (NRXN1) with nicotine dependence in European- and African-American smokers.

The neurexin-1 gene (NRXN1) has been shown to play a fundamental role in synaptogenesis and synaptic maintenance, as well as Ca(2+) channel and NMDA receptor recruitment. A recent study reported that NRXN1 is associated with nicotine dependence (ND); this, together with the intriguing physiological functions of the gene, motivated us to investigate the involvement of NRXN1 with ND in independent samples. In this study, we analyzed 21 single nucleotide polymorphisms (SNPs) within NRXN1 for association with ND, which was assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerström test for ND (FTND).