Avian Models with Spontaneous Autoimmune Diseases

Abstract

Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible any more. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models -albeit rare -reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present review describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and 206) with a scleroderma-like disease and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome.

Animal Models of Systemic Sclerosis

“…Subcutaneous adipose tissue is often replaced by collagen. UCD-200 chickens also produce autoantibodies, especially antinuclear, anti-centromere, and anti-phospholipid antibodies, rheumatoid factor, and antibodies to endothelial cells [74,75]. UCD-206 chickens are similar to the chickens of the line UCD-200.…”

“…There is also an internal organ involvement, particularly of the esophagus, heart, lung, and kidneys and an increased mortality. At around sixth week of age, the chickens develop glomerulonephritis and pericarditis [73,74]. Histopathological changes are similar to those in SSc and include massive perivascular mononuclear infiltrates, particularly of T and B lymphocytes and deposition of ECM components by activated fibroblasts, signs of obliterative vasculopathy, and apoptosis of endothelial cells with loss of functional capillaries [73].…”

Application of Animal Biomodel using Poultry: A Review

“…가축 및 인간의 연구모델로써 닭의 장점 계통분류학 연구에서 조류는 어류와 포유류의 사이에 위 치하고, 310만 년 전에 분화된 것으로 추정되며, 포유류에 더 욱 가까운 유전적 거리를 가지고 있는 것으로 나타나 있다 (Wick et al, 2006). 따라서 조류는 포유류와 유사한 생물학 적 특성과 척추동물의 진화에 중요한 동물로 인식되고 있으 며, 이러한 특성은 인간을 비롯한 가축의 특정 표현형 형질 에 대한 모델동물로써 활용이 가능하다는 것을 알 수 있다.…”

“…이러한 현상은 UDC-200 닭에서 나타나고 있으며, 인간의 SSh 와 유사한 특징을 가지고 있는 유일한 모델동물로, 혈관폐 색, 피부와 내장의 혈관주위 림프구 침윤, 피부 및 내부 장 기의 항체 섬유화 및 말초 다발성 관절염의 특성을 가지고 있다 (Beyer et al, 2010;Wick et al, 2006). 이 닭의 경우, 다 양한 섬유화 진행이 1∼3주 이후 진행되기 시작해 신속하게 내부 장기로 퍼져나가 5주가 경과하면 몸 전체의 90% 영역 에 나타나는 것으로 알려져 있고, 면역형광물질을 이용해 각 각의 특징을 분석한 결과도 보고된 바 있다 (Cipriani et al, 2016;Sgonc and Wick, 2008).…”

Self and non-self

“…Also, as part of our research on the immunological basis of fibrosis, Roswitha Sgonc, a long-term member of my group, in cooperation with Eric Gershwin, University of California at Davis (UCD) is successfully continuing comparative studies in an avian model with a spontaneous disease resembling human scleroderma, the UCD-200 line of chickens [34]. First in this model, and then corroborated in human patients, we made the important discoveries that (a) autoantibody-induced endothelial apoptosis rather than perivascular mononuclear cell infiltration is the first pathogenetic process in this crippling disease, and (b) post-inflammatory fibrosis is due to a lack of the anti-fibrotic cytokine transforming growth factor b2 (TGFb2).…”