Genetic mapping and evaluation of candidate genes for spasmodic, a neurological mouse mutation with abnormal startle response.
Genetic mapping and evaluation of candidate genes for spasmodic, a neurological mouse mutation with abnormal startle response.
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痉挛性候选基因的遗传图谱和评估，痉挛性是一种具有异常惊吓反应的神经系统小鼠突变。
DOI：
10.1006/geno.1993.1322
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发表时间：
1993
期刊：
影响因子：
4.4
通讯作者：
Camper,SA
中科院分区：
文献类型：
--
作者：
Buckwalter,MS;Testa,CM;Noebels,JL;Camper,SA
痉挛症（spd）是一种隐性突变的小鼠，其特征是翻正反射延长、精细运动震颤、腿紧握和僵硬。利用分离spd的亚种间回交，我们将spd置于Chr 11上，基因顺序如下：Adra-1-3.8 ± 2.1 cM-Pad-1-6.3 ± 2.7-（spd，Anx-6，Csfgm，Glr-1，Il-3，Il-4，Il-5，Sparc）-9.1 ± 2.4-D11 Mit 5 -2.2 ± 1.5-Asgr-1。这种定位排除了α1肾上腺素能受体（Adra-1）和GABA A受体α 1和γ 2亚基作为候选基因。另外两个有希望的候选基因，膜联蛋白VI（Anx-6）和谷氨酸受体（Glr-1），被定位在2.1 cM的该位点。虽然没有观察到spdandAnx-6或Glr-1之间的重组，没有证据表明在任何一个基因的病变。通过北方印迹分析、原位杂交和DNA序列分析证实了正常Anx-6和Glr-1 mRNA转录本的存在。Anx-6和Glr-1的定位扩展了人类染色体5 q21-q31和小鼠Chr 11之间已知的同线性同源性，并揭示了人类spd对应物的可能染色体定位。同线性同源性和表型相似性表明，痉挛小鼠可能是遗传性人类惊吓疾病，hyperekplexia（STHE）的遗传模型。
Spasmodic (spd) is a recessive mouse mutation characterized by a prolonged righting reflex, fine motor tremor, leg clasping, and stiffness. Using an intersubspecific backcross that segregatesspd, we placedspdon Chr 11 with the following gene order:Adra-1-3.8 ± 2.1 cM-Pad-1-6.3 ± 2.7-(spd, Anx-6, Csfgm, Glr-1, Il-3, Il-4, Il-5, Sparc)-9.1 ± 2.4-D11 Mit5-2.2 ± 1.5-Asgr-1. This localization eliminated the α1-adrenergic receptor (Adra-1) and the α1and γ2subunits of the GABAAreceptor as candidate genes. Two other promising candidate genes, annexin VI (Anx-6) and a glutamate receptor (Glr-1), were mapped to within 2.1 cM of thespdlocus. Although no recombination was observed betweenspdandAnx-6orGlr-1, no evidence was obtained for a lesion in either gene. The presence of normalAnx-6andGlr-1mRNA transcripts was confirmed by Northern blot analysis,in situhybridization, and DNA sequence analysis. The localization ofAnx-6andGlr-1extends the known synteny homology between human chromosome 5q21-q31 and mouse Chr 11 and reveals the probable chromosomal location of the human counterpart tospd. Synteny homology and phenotypic similarities suggest that spasmodic mice may be a genetic model for the inherited human startle disease, hyperekplexia (STHE).