Mutation of the trkB gene encoding the high-affinity receptor for brain-derived neurotrophic factor in stroke-prone spontaneously hypertensive rats.
Brain-derived neurotrophic factor and its receptor, trkB, are thought to play a crucial role for protection against neuronal death induced by brain ischemia, such as in stroke. In the present study we found a missense mutation in the trkB gene from all of the five substrains of stroke-prone spontaneously hypertensive rats (SHRSP) that were examined. This mutation was not found in six out of seven hypertensive but stroke-resistant ancestral strains (SHR) of SHRSP, nor in any of seven strains of normotensive, non-stroke-prone strains. Hippocampal neurons, which are particularly vulnerable to damage in stroke, were shown to be more susceptible to ischemic damage in SHRSP than in either SHR or normotensive, stroke-resistant controls. The association of a mutated trkB gene with the stroke-prone genotype found in this study suggests that the trkB gene merits further study as a promising candidate gene for stroke.
Kageyama
H
H
Laboratory of Health Science, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, 422, Japan. nemoto@ys7.u-shizuoka.ken.ac.jp
Nemoto
K
K
Nemoto
F
F
Sekimoto
M
M
Nara
Y
Y
Nabika
T
T
Iwayama
Y
Y
Fukamachi
K
K
Tomita
I
I
Senba
E
E
Forehand
C J
CJ
Hendley
E D
ED
Ueyama
T
T
D000818:Animals; D001923:Brain Chemistry; D002561:Cerebrovascular Disorders / Q000235:genetics*; D009154:Mutation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*
D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor