Transgenic mice with a mutated collagen promoter display normal response during bleomycin‐induced fibrosis and possess neurological abnormalities
Transgenic mice with a mutated collagen promoter display normal response during bleomycin‐induced fibrosis and possess neurological abnormalities
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胶原蛋白启动子突变的转基因小鼠在博来霉素诱导的纤维化过程中表现出正常反应，并具有神经系统异常
DOI：
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发表时间：
2000
影响因子：
4
通讯作者：
Barbara D. Smith
中科院分区：
文献类型：
--
作者：
J. H. Stoddart;D. Ladd;R. Bronson;Michael Harmon;James Jaworski;Carole Pritzker;Niels Lausen;Barbara D. Smith
We have previously identified a potential TGF‐β activation element (TAE) in the rat collagen α1(I) promoter at −1624 upstream of the transcriptional start site [Ritzenthaler et al., 1991, 1993]. To determine the importance of the TAE in vivo, we produced transgenic mice carrying 3.6 kb of the rat collagen α1(I) promoter linked to the reporter gene chloramphenicol acetyl transferase with and without site‐directed mutations that eliminate DNA‐protein binding at the TAE site. Tissue‐specific expression of the reporter gene in transgenic mice with the mutated collagen promoter was similar to that of transgenic mice with the normal promoter in two genetic backgrounds as judged by in situ hybridization, reporter assays, and immunochemistry. Endotracheal instillation of bleomycin induces lung fibrosis, mediated in part by TGF‐β. Earlier studies indicated that expression of wild‐type collagen‐reporter gene was upregulated in transgenic mice lungs in response to endotracheal instillation of bleomycin. A similar level of reporter gene upregulation was observed in transgenic mice carrying the mutation in the TAE. Two lines of transgenic mice carrying the mutated promoter construct displayed unexpected neurological abnormalities. In the FVB genetic background, there was a higher than normal incidence of mortality, spontaneous seizures, and an inability to nurture offspring. Histological evidence demonstrated clear abnormalities, including disorderly arrangement of neurons in the hippocampus and significant laminar cortical necrosis in the cerebrum in animals after seizures. In the C57Bl/6 background, there was a high incidence of severe communicating hydrocephalus, early runting, and increased mortality similar to that in transgenic animals with astroglial overexpression of TGF‐β. These animals provide an interesting model system to investigate molecular mechanisms responsible for seizures and hydrocephalus. J. Cell. Biochem. 77:135–148, 2000. © 2000 Wiley‐Liss, Inc.
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高度保守的内含子序列参与 α1(I) 胶原蛋白基因的转录调控。
DOI：
10.1091/mbc.1.6.487
发表时间：
1990
期刊：
Cell regulation
影响因子：
--
作者：
Liska,DJ;Slack,JL;Bornstein,P
通讯作者：
Bornstein,P
Col1a1 基因中有针对性的内含子缺失的小鼠对博来霉素诱导的肺纤维化有反应，突变等位基因的表达增加。
DOI：
10.1016/s0945-053x(99)00017-7
发表时间：
1999
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Hormuzdi,SG;Strandjord,TP;Madtes,DK;Bornstein,P
通讯作者：
Bornstein,P
影响因子：
6.5
作者：
Chen, SJ;Yuan, WH;Varga, J
通讯作者：
Varga, J
DOI：
10.1111/1523-1747.ep12606979
发表时间：
1995-05
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Kai Zhang;Warren L. Garner;Leslie Cohen;Jorge L. Rodriguez;S.e.m. Phan
通讯作者：
Kai Zhang;Warren L. Garner;Leslie Cohen;Jorge L. Rodriguez;S.e.m. Phan
影响因子：
10
作者：
GIRI, SN;HYDE, DM;HOLLINGER, MA
通讯作者：
HOLLINGER, MA