Favello A et al. (1995) Methods Cell Biol "Genomic DNA sequencing methods."

Wilson RK, Hillier L, Favello A

[Methods Cell Biol, 1995]

Sequence analysis of cosmids from C. elegans and other organisms currently is best done using the random or "shotgun" strategy (Wilson et al., 1994). After shearing by sonication, DNA is used to prepare M13 subclone libraries which provide good coverage and high-quality sequence data. The subclones are assembled and the data edited using software tools developed especially for C. elegans genomic sequencing. These same tools facilitate much of the subsequent work to complete both strands of the sequence and resolve any remaining ambiguities. Analysis of the finished sequence is then accomplished using several additional computer tools including Genefinder and ACeDB. Taken together, these methods and tools provide a powerful means for genome analysis in the nematode.

Reed E et al. (2018) J Neurochem "Animal models of Wilson disease."

Lutsenko S, Bandmann O, Reed E

[J Neurochem, 2018]

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism manifesting with hepatic, neurological and psychiatric symptoms. The limitations of the currently available therapy for WD (particularly in the management of neuropsychiatric disease), together with our limited understanding of key aspects of this illness (e.g. neurological vs hepatic presentation) justify the ongoing need to study WD in suitable animal models. Four animal models of WD have been established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b knockout mouse and the Labrador retriever. The existing models of WD all show good similarity to human hepatic WD and have been helpful in developing an improved understanding of the human disease. As mammals, the mouse, rat and canine models also benefit from high homology to the human genome. However, important differences exist between these mammalian models and human disease, particularly the absence of a convincing neurological phenotype. This review will first provide an overview of our current knowledge of the orthologous genes encoding ATP7B and the closely related ATP7A protein in C. elegans, Drosophila and zebrafish (Danio rerio) and then summarise key characteristics of rodent and larger mammalian models of ATP7B-deficiency. This article is protected by copyright. All rights reserved.

Cerpa W et al. (2005) Mol Aspects Med "Is there a role for copper in neurodegenerative diseases?"

Cerpa W, Inestrosa NC, Varela-Nallar L, Minniti AN, Reyes AE

[Mol Aspects Med, 2005]

Copper is an essential metal in living organisms; thus, the maintenance of adequate copper levels is of vital importance and is highly regulated. Dysfunction of copper metabolism leading to its excess or deficiency results in severe ailments. Two examples of illnesses related to alterations in copper metabolism are Menkes and Wilson diseases. Several proteins are involved in the maintenance of copper homeostasis, including copper transporters and metal chaperones. In the last several years, the beta-amyloid-precursor protein (beta-APP) and the prion protein (PrP(C)), which are related to the neurodegenerative disorders Alzheimer and prion diseases respectively, have been associated with copper metabolism. Both proteins bind copper through copper-binding domains that also have been shown to reduce copper in vitro. Moreover, this ability to reduce copper is associated with a neuroprotective effect exerted by the copper-binding domain of both proteins against copper in vivo. In addition to a functional link between copper and beta-APP or PrP(C), evidence suggests that copper has a role in Alzheimer and prion diseases. Here, we review the evidence that supports both, the role of beta-APP and PrP(C), in copper metabolism and the putative role of copper in neurodegenerative diseases.

Emmons SW (1987) Cell "Mechanisms of C. elegans development."

Emmons SW

[Cell, 1987]

What are the respective roles in multicellular development of mechansims acting at the level of the cell and mechanisms acting at the level of the cell group? It's an old question, and one that is central to the problem of developmental biology. Even early in this century it had long been debated "whether the character of growth and morphogenesis is a cause or a result of the corresponding activities on the part of the component cells individually considered" (E.B. Wilson, The Cell in Development and Heredity, Macmillan, 1925, p. 1029). The question is now being reexamined in the nematode Caenorhabditis elegans, an organism whose embryonic and postembryonic development are easily observed. Initial studies emphasized the reproducibility and, thus, the apparent cell-autonomy of development in the animal. Little flexibility in cell division patterns or differentiation was found in blastomere isolation experiments or after microsurgery with a laser beam. More recent results, however, demonstrate that cellular interactions are more important. These new results, combined with new molecular techniques that make it possible to isolate genes defined by mutations and to reintroduce cloned genes into the germ line, open the way to a molecular analysis of developmental mechanisms that are likely to be widespread in the animal kingdom.