There was no significant relationship between the survival rate in dogs with nonseptic SIRS or sepsis and the initial serum CRP concentrations. There was a correlation between decreasing CRP concentrations and recovery from disease. However, the changes in CRP concentrations over a 3-day period correctly predicted survival in 94% of dogs and death in 30% of the dogs (false positive rate 22%).

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The development, progression, and recurrence of autoimmune diseases are frequently driven by a group of participatory autoantigens. We identified and characterized novel autoantigens by analyzing the autoantibody binding pattern from horses affected by spontaneous equine recurrent uveitis to the retinal proteome. Cellular retinaldehyde-binding protein (cRALBP) had not been described previously as autoantigen, but subsequent characterization in equine recurrent uveitis horses revealed B and T cell autoreactivity to this protein and established a link to epitope spreading. We further immunized healthy rats and horses with cRALBP and observed uveitis in both species with typical tissue lesions at cRALBP expression sites.

Gene targeting by homologous recombination or by sequencespecific nucleases allows the precise modification of genomes and genes to elucidate their functions. Although gene targeting has been used extensively to modify the genomes of mammals, fish, and amphibians, a targeting technology has not been available for the avian genome. Many of the principles of humoral immunity were discovered in chickens, yet the lack of gene targeting technologies in birds has limited biomedical research using this species. Here we describe targeting the joining (J) gene segment of the chicken Ig heavy chain gene by homologous recombination in primordial germ cells to establish fully transgenic chickens carrying the knockout. In homozygous knockouts, Ig heavy chain production is eliminated, and no antibody response is elicited on immunization. Migration of B-lineage precursors into the bursa of Fabricius is unaffected, whereas development into mature B cells and migration from the bursa are blocked in the mutants. Other cell types in the immune system appear normal. Chickens lacking the peripheral B-cell population will provide a unique experimental model to study avian immune responses to infectious disease. More generally, gene targeting in avian primordial germ cells will foster advances in diverse fields of biomedical research such as virology, stem cells, and developmental biology, and provide unique approaches in biotechnology, particularly in the field of antibody discovery.B-cell development | avian immunology | genome editing T he chicken has historically been an important model vertebrate organism in the fields of developmental biology and immunology and has contributed a number of basic tenets to these fields. For example, B lymphocytes were first recognized in chickens as the antibody-producing cells and are named after the bursa of Fabricius, a gut-associated lymphoid tissue (GALT) that is required for B-cell development in chickens (1). Graft-versushost response was first described in chicken embryos (2), and the first attenuated vaccine was developed by Louis Pasteur against fowl cholera caused by Pasteurella multocida. Nevertheless, the lack of a robust genome editing technology including knockouts has put the chicken at a distinct disadvantage to mammalian species, especially the mouse, as a vertebrate animal model. The discovery of ES cells provided a powerful method to make desired changes to genes of interest in the mouse using homologous recombination, but interestingly, ES cells have not been as easily derived from other species. In the case of chickens, ES cells can contribute to all somatic lineages in high-grade chimeras, but germ-line transmission has not yet been demonstrated, precluding their use in creating fully transgenic chickens (3). Although ES cells are not germ line competent in chickens, embryo-derived primordial germ cells (PGCs) can be cultured indefinitely, transfected, clonally selected, and reintroduced into the embryo where they colonize the gonad and give rise to fully transgenic progeny ...