Mutations in ric-3 (resistant to inhibitors of cholinesterase) suppress the neuronal degenerations caused by a gain of function mutation in the Caenorhabditis elegans DEG-3 acetylcholine receptor. RIC-3 is a novel protein with two transmembrane domains and extensive coiled-coil domains. It is expressed in both muscles and neurons, and the protein is concentrated within the cell bodies. We demonstrate that RIC-3 is required for the function of at least four nicotinic acetylcholine receptors. However, GABA and glutamate receptors expressed in the same cells are unaffected. In ric-3 mutants, the DEG-3 receptor accumulates in the cell body instead of in the cell processes. Moreover, co-expression of ric-3 in Xenopus laevis oocytes enhances the activity of the C.elegans DEG-3/DES-2 and of the rat a-7 acetylcholine receptors. Together, these data suggest that RIC-3 is speci®cally required for the maturation of acetylcholine receptors.

Hedgehog (Hh) signals regulate invertebrate and vertebrate development, yet the role of the cascade in adipose development was undefined. To analyze a potential function, we turned to Drosophila and mammalian models. Fat-body-specific transgenic activation of Hh signaling inhibits fly fat formation. Conversely, fat-body-specific Hh blockade stimulated fly fat formation. In mammalian models, sufficiency and necessity tests showed that Hh signaling also inhibits mammalian adipogenesis. Hh signals elicit this function early in adipogenesis, upstream of PPARgamma, potentially diverting preadipocytes as well as multipotent mesenchymal prescursors away from adipogenesis and toward osteogenesis. Hh may elicit these effects by inducing the expression of antiadipogenic transcription factors such as Gata2. These data support the notion that Hh signaling plays a conserved role, from invertebrates to vertebrates, in inhibiting fat formation and highlighting the potential of the Hh pathway as a therapeutic target for osteoporosis, lipodystrophy, diabetes, and obesity.

No abstract

In mammals, Mda5 and RIG-I are members of the evolutionary conserved RIG-like helicase family that play critical roles in the outcome of RNA virus infections. Resolving influenza infection in mammals has been shown to require RIG-I; however, the apparent absence of a RIG-I homolog in chickens raises intriguing questions regarding how this species deals with influenza virus infection. Although chickens are able to resolve certain strains of influenza, they are highly susceptible to others, such as highly pathogenic avian influenza H5N1. Understanding RIG-like helicases in the chicken is of critical importance, especially for developing new therapeutics that may use these systems. With this in mind, we investigated the RIG-like helicase Mda5 in the chicken. We have identified a chicken Mda5 homolog (ChMda5) and assessed its functional activities that relate to antiviral responses. Like mammalian Mda5, ChMda5 expression is upregulated in response to dsRNA stimulation and following IFN activation of cells. Furthermore, RNA interference-mediated knockdown of ChMda5 showed that ChMda5 plays an important role in the IFN response of chicken cells to dsRNA. Intriguingly, although ChMda5 levels are highly upregulated during influenza infection, knockdown of ChMda5 expression does not appear to impact influenza proliferation. Collectively, although Mda5 is functionally active in the chicken, the absence of an apparent RIG-I–like function may contribute to the chicken’s susceptibility to highly pathogenic influenza.

In 2004 the chicken genome sequence and more than 2.8 million single nucleotide polymorphisms (SNPs) were reported. This information greatly enhanced the ability of poultry scientists to understand chicken biology, especially with respect to identification of quantitative trait loci (QTL) and genes that control simple and complex traits. To validate and address the quality of the reported SNPs, assays for 3072 SNPS were developed and used to genotype 2576 DNAs isolated from commercial and experimental birds. Over 90% of the SNPs were valid based on the criterion used for segregating, and over 88% had a minor allele frequency of 2% or greater. As the East Lansing (EL) and Wageningen University (WAU) reference panels were genotyped, 1933 SNPs were added to the chicken genetic map, which was used in the second chicken genome sequence assembly. It was also discovered that linkage disequilibrium varied considerably between commercial layers and broilers; with the latter having haplotype blocks averaging 10 to 50 kb in size. Finally, it was estimated that commercial lines have lost 70% or more of their genetic diversity, with the majority of allele loss attributable to the limited number of chicken breeds used.

Avian leukosis virus subgroup J (ALV-J) is the newest member of the avian oncogenic retroviruses. After the first isolation of the ALV-J prototype virus, HPRS-103, more than 10 years ago in the United Kingdom (21), viruses belonging to this subgroup have spread rapidly to many countries, becoming one of the major pathogens facing the broiler meat industry worldwide (26). The env gene of ALV-J is closely related to that of a novel group of chicken endogenous retroviral elements designated EAV-HP (24), suggesting that ALV-J has emerged by genetic recombination (17). Compared to the pathogenic ALV subgroups, such as A and B, which primarily induce lymphoid leukosis in genetically susceptible birds (18), ALV-J isolates predominantly induce myeloid leukosis (ML), a property thought to be associated with their tropism for the cells of the myeloid lineage (1). Previous studies have shown that HPRS-103 and other ALV-J isolates do not transform chicken bone marrow cell cultures in vitro and that the tumors induced by these viruses occur after long latent periods (19). These observations and the demonstration that the nucleotide sequence of the viral genome does not carry any viral oncogenes (2, 3) suggested that ALV-J-induced oncogenesis occurs by the activation of oncogenes through the mechanism of insertional mutagenesis (13).Although the tumors induced by HPRS-103 are of late onset, occurring at a median age of 20 weeks (19), we have previously shown that acutely transforming ALVs that induce rapid-onset tumors could be isolated from about 60% of lateonset tumors (20). Many tumors obtained from field cases of ML also contained acutely transforming viruses, suggesting that generation of acutely transforming ALVs is a common feature of ALV-J-induced oncogenesis. Most of these virus isolates were able to transform chicken bone marrow or monocyte cell cultures in vitro and induce rapid-onset tumors when inoculated into susceptible birds, a property attributed to the transduction of oncogenes. The acutely transforming ALV-J strain 966 was recovered from a myeloid tumor induced experimentally by . This virus transformed peripheral blood monocyte and bone marrow cells and induced rapid-onset tumors in chickens (20) and turkeys (28). Peripheral blood monocytes and bone marrow cells from different lines of chickens showed variation in the relative susceptibility to transformation by ALV-J strain 966 (1). This variation was correlated with the relative susceptibility to the induction of ML by HPRS-103, suggesting the involvement of common cell-specific viral and/or host factors in oncogenesis induced by these two viruses. In order to identify the viral genes and oncogenes that are involved in the rapid induction of tumors, we have determined the complete sequence of the proviral genome of ALV-J strain 966. In this paper, we demonstrate the genome structure of the provirus of the 966 strain of ALV-J and compare its sequence with that of HPRS-103 and other acutely transforming avian retroviruses. We also present data demonstratin...

Genetic progress in poultry species for meat production has contributed to the consistent growth in world production of poultry meat. The poultry species have a number of advantages over the larger species used for meat production. It is possible to maintain large pedigreed populations and use their high reproductive rates to transfer genetic progress to the production generations in less than five years. These populations continue to maintain high heritabilities despite, in some cases, prolonged selection. The history of selection progress in broiler chickens (Gallus gallus domesticus) is reviewed and compared with rates of progress in the duck (Anas platyrhyncos) and the turkey (Meleagris gallopavo).The rates of genetic change for production traits such as growth, feed efficiency and yield have changed the physiology of the birds. Changes in selection criteria have been made to improve the robustness of the production stock. This allows them to perform well in a wider range of environments. These have been combined with improved definitions of the optimum environments for the birds to minimise any impact on welfare and health. This paper describes examples of selection in the broiler chicken aimed at improving skeletal quality and resistance to ascites. A number of the factors influencing future selection criteria are discussed. Breeding programmes have adapted to respond quickly to adverse genetic correlated responses. The need to combine selection for a large number of traits requires that the programmes are very efficient and use the best statistical techniques available for multivariate breeding value estimation.

Genetically improved strains of poultry have been a major contribution to the success of the poultry industry, which is a major source of animal protein for the human population in most countries of the world. Improvements in health, nutrition and environmental management have also contributed to improved performance, but the majority of the change has been attributed to genetic improvement. Egg production has been improved consistently since the late 1930s, and the industry continues to improve the efficiency of laying hen production by at least 1% per year. This requires the simultaneous improvement of multiple traits, including egg number, egg size, liveability, persistency and mature body weight. There is also continuing progress in uniformity of egg size and colour and freedom from defects. In broilers, combined selection for growth, body composition, feed efficiency and liveability continues to deliver 2-3% improvement per year in the efficiency of meat production. Other traits such as robustness, specific and general disease resistance, and absence of metabolic defects have also contributed to this progress.