Abstract
Each day our cells degrade chromosomal DNA from billions of apoptotic cells and extruded nuclei of erythrocyte precursors. Enzymatic degradation is carried out by DNaseII in macrophages that have ingested the DNA. Recent work shows that suppression of DNaseII results in polyarthritis in a mouse model, and this disease strongly resembles human rheumatoid arthritis. DNaseII−/−IFN-IR−/− mice as well as mice with an inducible deletion in DNaseII all developed synovial hyperplasia, pannus formation with abundant CD68+ macrophages, cartilage erosion, and bone lysis in multiple joints. Furthermore, macrophages with undigested DNA produced large amounts of TNF-alpha and other pro-inflammatory cytokines. Treatment with an anti-TNF-alpha antibody prevented the development of polyarthritis. This should prove to be a useful model for the study of rheumatoid arthritis and other autoimmune conditions.
Kawane K, Ohtani M, Miwa K, et al. Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature
Alopecia is a common problem in domestic animals, and one that causes their owners great concern. Although most cases represent acquired alopecia, congenital alopecia also occurs. In this article, Lars Mecklenburg reviews what is known about congenital alopecia in dogs, cats, horses, cattle, and swine. In addition, he provides a very nice update on hair follicle morphogenesis and molecular signaling involved in hair development. This comprehensive review will help the reader distinguish between congenital alopecia caused by defects in hair follicle and hair shaft development from those cases caused by neuroectodermal dysplasias.
Mecklenburg L. An overview on congenital alopecia in domestic animals. Vet Dermatol
Horses develop a number of disorders in which eosinophils play a central role, such as hypersensitivity reactions, neoplasia, parasitic infestations, and autoimmune diseases. CCL11 (eotaxin) is a potent mediator of eosinophil migration when bound to its receptor CCR3. Increased knowledge of eosinophil biology may lead to improved treatments for eosinophil-related conditions. Weston et al cloned the equine CCR3 cDNA and performed in situ hybridization to determine the tissue distribution of CCR3-positive cells in normal horses. The majority of positive cells in the colon were eosinophils, located mainly in the lamina propria. In contrast, the majority of CCR3 positive cells in the lung and spleen were lymphocytes. Interestingly, except for the colon, expression of CCR3 mRNA did not correlate with expression of CCL11 mRNA. This may be due to the fact that CCR3 has ligands other than CCL11. CCR3 expression was not detected in the normal skin examined, nor did the normal skin contain eosinophils.
Weston MC, Cunningham FM, Collins ME. Distribution of CCR3 mRNA expression in horse tissues. Vet Immunol Immunopathol
The choice of an appropriate reference gene for real-time PCR experiments is critical for accurate interpretation of the results. Recently, several groups have pointed out the inadequacies in using a single reference gene, especially when cells are subjected to experimental manipulation. Robinson and colleagues used three different programs to evaluate the usefulness of four candidate genes in bovine blood from normal animals and animals infected with Boophilus microplus. Expression levels of the GAPDH, 18S rRNA, RPLP0 and β-actin genes were analyzed with the Bestkeeper, Norm Finder, and geNorm programs. The β-actin and GAPDH genes were determined to be the most suitable reference genes in this experiment, while RPLP0 was the least stably expressed. 18S rRNA was expressed at such a high level that it was deemed unsuitable for experiments in which the gene(s) of interest is expressed at low levels. The use of multiple reference genes should be strongly considered in designing real-time PCR experiments.
Robinson TL, Sutherland IA, Sutherland J. Validation of candidate bovine reference genes for use with real-time PCR. Vet Immunol Immunopathol
Lipoxygenases play a role in cardiovascular disease by enabling cholesterol deposition and inflammation in coronary arteries. Investigators using 12/15-lipoxygenase knock-out mice made a surprising finding related to cancer. When they noticed splenomegaly in their mice they discovered that the mice had a myeloproliferative disease similar to chronic myeloid leukemia. They propose that the absence of 12/15-lipoxygenase results in increased activation of the PI3-kinase pathway and reduced nuclear accumulation of interferon consensus sequence binding protein, which then allows increased expression of the oncoprotein Bcl-2. Most mouse models of chronic myeloid leukemia quickly progress to blast crisis and do not reflect the lengthy chronic phase that is present in humans and the 12/15 knock-out mice. The authors point out that these knock-out mice were developed ten years ago, but splenomegaly and myeloproliferative disease has not been previously reported. One possible explanation is that researchers were focused on the cardiovascular system and failed to notice the splenomegaly and related signs of myeloproliferative disease.
Middleton MK, Zukas AM, Rubinstein T. Identification of 12/15-lipoxygenase as a suppressor of myeloproliferative disease. J Exp Med