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FIBROTIC NON-HUMAN ANIMAL, AND USE THEREOF

Foreign code F200010105
File No. 3667
Posted date May 18, 2020
Country WIPO
International application number 2013JP079623
International publication number WO 2014069597
Date of international filing Oct 31, 2013
Date of international publication May 8, 2014
Priority data
  • 201261721301 (Nov 1, 2012) US
Title FIBROTIC NON-HUMAN ANIMAL, AND USE THEREOF
Abstract The present invention provides a non-human animal IKKβ characterized by developing tissue fibrosis and being produced by deleting IKKβ gene in a myofibroblast- and/or smooth-muscle-cell-specific manner. The non-human animal develops a disease condition that is highly similar to scleroderma. Thus, the non-human animal can be used as a model animal for scleroderma and therefore is extremely useful.
Outline of related art and contending technology BACKGROUND ART
The deposition of collagen fibers is associated with tissue fibrosis, inflammatory response in vivo as a final image phenomenon occurs in the wound healing processes, such as wound is cured, to play an important role in vivo. On the other hand, the excessive tissue fibrosis, inflammation of a variety of diseases based, for example, skin diseases, heart disease, respiratory diseases, autoimmune disease, collagen disease, cancer, arteriosclerosis, diabetes and the like, of delaying the onset or exacerbation of the disease are factors. In addition, the mechanism of fibrosis is not a well - defined, fibrosis associated with the treatment of these diseases is difficult.
Collagen is one of scleroderma (systemic scleroderma) is, the synthesis of collagen fibers in the skin and enhance a visceral accumulation and mainly composed of a disease. The disease is characterized in that, in a ratio of about 1:9 men and women predominantly many, of the age is 30-50 is found in mid-age of twenties RVDS. In addition, the pathological condition is, Raynaud's symptoms, other skin lesions such as induration of the skin, pulmonary fibrosis, renal dysfunction, such as esophageal visceral disease also adversely affected. Therefore, quality of life as well as scleroderma, affects the life prognosis and intractable, current, or the like may also effective treatment has not been established.
Conventional, fibrosis, in animal models of scleroderma may be used as is, or drugs such as bleomycin (transforming growth factor beta) TGF β, CTGF (connective tissue growth factor), cytokines such as bFGF (basic fibroblast growth factor) artificially by administration of a mouse resulted in fibrosis (non-patent document 1, 2), or, due to genetic abnormality in the Tight skin mouse Fibrillin-1 (non-patent document 3, 4). However, these animal models is known, for example skin mice receiving cytokines locally at the site of administration to the skin and cures, male and female is about the same Tight skin mouse skin appreciably, esophageal renal failure or the like is not observed, such that there is a problem. Therefore, the model animal known scleroderma, similarity of both pathologies in human beings, and the like of the artificial surface may not be sufficient. In addition, in recent years Fibrillin-1 is scleroderma is completely different from the genetic disease Stiff Skin Syndrome is the causal genes has been reported (non-patent document 5) from the, scleroderma Tight skin mouse model mouse of the usefulness as a question has been developed.
Scope of claims (In Japanese)[請求項1]
 筋線維芽細胞及び/又は平滑筋細胞特異的にIKKβ遺伝子を欠損した、組織の線維化を示す非ヒト動物又はその生体の一部。

[請求項2]
 組織の線維化が、自己免疫疾患、膠原病、皮膚疾患、心疾患、呼吸器系疾患、食道疾患、胃腸疾患、肝疾患、腎疾患、脳神経疾患、癌及び糖尿病からなる群より選択される疾患に伴う線維化を再現することを特徴とする、請求項1に記載の非ヒト動物又はその生体の一部。

[請求項3]
 強皮症モデルである、請求項1に記載の非ヒト動物又はその生体の一部。

[請求項4]
 動物がげっ歯類である、請求項1に記載の非ヒト動物又はその生体の一部。

[請求項5]
 組織の線維化の予防用及び/又は治療用の物質をスクリーニングする方法であって、
(a)請求項1に記載の非ヒト動物又はその生体の一部に試験物質を接触させる工程、及び
(b)前記非ヒト動物又はその生体の一部における組織の線維化を分析する工程
を含む前記方法。

[請求項6]
 強皮症の予防用及び/又は治療用の物質をスクリーニングする方法であって、
(a)請求項1に記載の非ヒト動物又はその生体の一部に試験物質を接触させる工程、及び
(b)前記非ヒト動物又はその生体の一部における強皮症の病態を反映する事象を分析する工程
を含む前記方法。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • KYOTO UNIVERSITY
  • THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
  • Inventor
  • ASHIDA, Noboru
  • YOKODE, Masayuki
  • KARIN, Michael
  • NGUYEN TIEN, Dat
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN TD TG
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