Psoriasis is a T-cell-mediated chronic inflammatory skin disease believed to be of autoimmune nature that can be triggered or worsened by streptococcal throat infections. In addition to conventional chronic inflammatory changes, psoriasis is characterized by complex and striking alterations in epidermal growth and differentiation. Psoriasis is generally not observed in animals other than man, and this lack of a suitable animal model has greatly hindered research into the pathogenesis of psoriasis. Multiple transgenic, knockout, and reconstituted models of psoriasis have been developed over the past two decades. Despite their limitations, these models have demonstrated that keratinocyte hyperplasia, vascular hyperplasia, and cell-mediated immunity in the skin are closely interrelated. Xenograft models, in which involved and uninvolved psoriatic skin are transplanted onto immunodeficient mice, are the only models that come close to incorporating the complete genetic, immunologic, and phenotypic changes of the disease. They have shown conclusively that psoriasis is a T-cell-mediated disease, and have been used to elucidate novel pathogenic pathways. In this review, we describe various animal models, detail the immunologic and intracellular pathways that mediate these phenotypes and assess the utility of these models to better understand this disease.
Wild-type (WT) NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) when given 0.05% NaI in their drinking water, whereas B cell–deficient NOD.H-2h4 mice are SAT resistant. To test the hypothesis that resistance of B cell–deficient mice to SAT was due to the activity of regulatory CD4+CD25+ T (T reg) cells activated if autoantigen was initially presented on non–B cells, CD25+ T reg cells were transiently depleted in vivo using anti-CD25. B cell–deficient NOD.H-2h4 mice given three weekly injections of anti-CD25 developed SAT 8 wk after NaI water. Thyroid lesions were similar to those in WT mice except there were no B cells in thyroid infiltrates. WT and B cell–deficient mice had similar numbers of CD4+CD25+Foxp3+ cells. Mice with transgenic nitrophenyl-specific B cells unable to secrete immunoglobulin were also resistant to SAT, and transient depletion of T reg cells resulted in severe SAT with both T and B cells in thyroid infiltrates. T reg cells that inhibit SAT were eliminated by day 3 thymectomy, indicating they belong to the subset of naturally occurring T reg cells. However, T reg cell depletion did not increase SAT severity in WT mice, suggesting that T reg cells may be nonfunctional when effector T cells are activated; i.e., by autoantigen-presenting B cells.
Background: The mouse is an important and widely utilized animal model for bone marrow transplant (BMT) translational studies. Here, we document the course of an unexpected increase in mortality of congenic mice that underwent BMT.Methods: Thirty five BMTs were analyzed for survival differences utilizing the Log Rank test. Affected animals were evaluated by physical examination, necropsy, histopathology, serology for antibodies to infectious disease, and bacterial cultures.Results: Severe bacteremia was identified as the main cause of death. Gastrointestinal (GI) damage was observed in histopathology. The bacteremia was most likely caused by the translocation of bacteria from the GI tract and immunosuppression caused by the myeloablative irradiation. Variability in groups of animals affected was caused by increased levels of gamma and X-ray radiation and the differing sensitivity of the two nearly genetically identical mouse strains used in the studies. Conclusion:Our retrospective analysis of thirty five murine BMTs performed in three different laboratories, identified C57BL/6NCr (Ly5.1) as being more radiation sensitive than B6.Cg-Ptprc a / NCr (Ly5.2). This is the first report documenting a measurable difference in radiation sensitivity and its effects between an inbred strain of mice and its congenic counterpart eventually succumbing to sepsis after BMT.
We report the complete genome sequence of Mycoplasma ovis strain Michigan. Its single circular chromosome has 702,511 bp and contains 2 copies of the 16S rRNA gene, one corresponding to M. ovis and the other to “Candidatus Mycoplasma haemovis.” All housekeeping genes and the 5S-23S rRNA genes are present in single copies.
SUMMARY We report a pedigree in which six males died of cardiac failure within the first eight months of life. These males were related through healthy females, as with X linked recessive inheritance. There was no consanguinity. None of the affected boys had an anatomical cardiac abnormality. In two affected brothers, histological evidence for endomyocardial fibroelastosis was documented, and in one of these electron microscopy demonstrated abnormalities of the mitochondria as found in mitochondrial cytopathy. A review of published reports revealed five similar X linked pedigrees, and in two of these mitochondrial abnormalities were found. We suggest that these families may show an X linked recessive cardiomyopathy with mitochondrial abnormalities.We present a family in which six males died of heart failure in infancy. Two of the infants, who were brothers, were found to have endomyocardial fibroelastosis (EMFE) at necropsy and abnormal mitochondria were found in one of these. Other male relatives who died of heart failure as infants had similar clinical courses, but were not given this specific diagnosis. The pedigree was compatible with X linked recessive inheritance of mitochondrial cardiomyopathy. Female
We studied the effects of acid mine drainage (AMD) from abandoned coal mines on lotic salamanders and environmental conditions in the upper watershed (Cumberland Plateau) of North Chickamauga Creek (NCC; Tennessee River drainage) in southeastern Tennessee, USA, from 1996-97. Study sites (2 nd -or 3 rd -order reaches) were sampled in an AMD-influenced section (five sites) and in two reference streams (two minimally disturbed sites). A total of 212 plethodontids (premetamorphic larvae) representing four species were collected by kicknetting in riffles (n ¼ 99) and electrofishing in mixed habitats (n ¼ 113). The dusky salamander (Desmognathus fuscus) was the most abundant species in both AMD and reference reaches (> 80 -90% of total catches), successively followed by the southern two-lined salamander (Eurycea cirrigera), spring salamander (Gyrinophilus porphyriticus), and red salamander (Pseudotriton ruber). Mining-influenced reaches were characterized by acidic flows (mean pH ¼ 3.8-5.6), zero to low alkalinity, and elevated conductivity, sulfate, hardness, aluminum, and manganese, as well as very low abundances of salamanders. Reference reaches were slightly acidic to circumneutral (mean pH ¼ 6.0-6.9) with low to moderate alkalinity, low levels of conductivity, hardness, sulfate, and metals, and high salamander abundances. Our findings document the impact of acid/metal pollution from past coal mining activities on lotic salamanders in a Cumberland Plateau stream.
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