Genomic analysis of collagen and endogenous virus loci in the UCD-200 and 206 lines of chickens, animal models for scleroderma.

Abstract

University of California at Davis (UCD) lines 200 and 206 chickens develop a hereditary systemic scleroderma-like connective tissue disease characterized by severe lymphocytic infiltration and excessive accumulation of collagen in skin and internal organs. The immune system seems to play an important role in the development and/or perpetuation of this condition. The main goal of our work with this strain is the investigation of interactions between endothelial cells, lymphocytes, macrophages and fibroblasts leading to the proliferation of the latter and to excessive collagen synthesis and/or deposition. One aim of the present study was to clarify whether UCD-200 and 206 chickens have a defect of collagen genes at the genomic level by means of restriction fragment length polymorphism (RFLP) analysis using non-radioactively labelled cDNA probes specific for chicken alpha 1(I), alpha 2(I), alpha 1(II), alpha 1(III), alpha 1(VI), alpha 2(VI), and alpha 3(VI) (pro) collagens. As in the human disease, no gross alteration at the genomic level of collagen genes has been found, thus providing the UCD-200/206 model to be appropriate for studying the altered collagen metabolism in systemic sclerosis (SSc). In addition to the RFLP analysis of procollagen genes, we investigated the endogenous avian leukosis virus loci (ev) of UCD-200 and 206 chickens by means of Southern blot analysis of Sac I and BamH I digested DNA samples using pRAV-2, a Rous sarcoma virus specific probe, for hybridization. Most UCD-200 and 206 chickens harbour evs 1, 3 and 10 similar to the healthy control UCD-058, but they also contain a novel ev characterized by a 4.2 kb Sac I fragment and a 6.1 kb BamH I fragment, which we would like to designate ev 23. So far, the role of ev 23 in the development of avian scleroderma is unclear; for further analysis classical crossbreeding experiments are necessary and are underway.