Stroke damage in mice after knocking the neutrophin-4 gene into the brain-derived neurotrophic factor locus

被引:20
作者
Endres, M
Fan, GP
Hirt, L
Jaenisch, R
机构
[1] Humboldt Univ, Dept Neurol, Charite Hosp, D-10117 Berlin, Germany
[2] Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA 90024 USA
[3] CHU Vaudois, Lab Rech Neurol, CH-1011 Lausanne, Switzerland
[4] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA
关键词
BDNF; cerebral ischemia; knock-in; neurotrophins; NT4;
D O I
10.1097/01.WCB.0000043949.67811.C6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Neurotrophins play a protective role during cerebral ischemia, and mice lacking both alleles for neurotrophin 4 (Nt4(-/-)) or deficient in a single allele for brain-derived neurotrophic factor (Bduf(+/-)) have increased susceptibility to cerebral ischemia. This study directly compared the biologic activities of brain-derived neurotrophic factor (BDNF) and NT4 by replacing the Bdnf coding sequence with the Nt4 sequence (Bdnf(+/nt4-ki)). Mice expressing one Nt4 allele in place of Bdnf develop 61% bigger lesions after 1-hour middle cerebral artery occlusion compared with wild-type littermates. Physiologic parameters did not contribute to ischemia susceptibility. In conclusion, NT4 is less potent than BDNF in promoting brain survival after stroke.
引用
收藏
页码:150 / 153
页数:4
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