Genetic basis of age-dependent synaptic abnormalities in the retina.
Genetic basis of age-dependent synaptic abnormalities in the retina.
复制标题
视网膜中年龄依赖性突触异常的遗传基础。
DOI：
10.1007/s00335-014-9546-7
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发表时间：
2015-02
期刊：
影响因子：
2.5
通讯作者：
Ikeda, Akihiro
中科院分区：
文献类型：
--
作者：
Higuchi, Hitoshi;Macke, Erica L.;Lee, Wei-Hua;Miller, Sam A.;Xu, James C.;Ikeda, Sakae;Ikeda, Akihiro
了解正常的衰老过程将有助于我们确定年龄相关疾病是如何引起和发展的机制。A/J近交系小鼠已经显示出在视网膜中表现出加速老化表型，包括增加的炎症和感光细胞变性，这类似于人类衰老症状。C57 BL/6 J（B6）近交系小鼠对这些异常不太敏感，表明存在影响其严重程度的遗传因素。在这项研究中，我们确定了另一个年龄依赖性表型，异位突触形成，也加速在A/J视网膜相比，B6视网膜。通过利用重组近交系的遗传作图，我们确定了7号和19号染色体上的数量性状位点（QTL），这些位点有助于异常视网膜突触以及其他年龄依赖性表型。利用其中一条染色体来自A/J，其余染色体组为B6的二体单染色体置换系，我们研究了每个QTL对视网膜老化表型的个体效应。我们观察到，这两个QTL独立地有助于异常视网膜突触，减少视锥细胞的数量，和上调视网膜应激标志物，胶质细胞酸性蛋白（GFAP）。在19号染色体上具有单个染色体取代的小鼠也表现出炎症细胞的增加，这是衰老和年龄相关性黄斑变性的特征。因此，我们确定了能够独立影响小鼠年龄依赖性视网膜异常的严重程度和进展的QTL。
Understanding the normal aging process will help us determine the mechanisms of how age-related diseases are caused and progress. A/J inbred mice have been shown to exhibit accelerated aging phenotypes in the retina including increased inflammation and photoreceptor cell degeneration, which resemble human aging symptoms. C57BL/6J (B6) inbred mice are less susceptible for these abnormalities, indicating the existence of genetic factor(s) that affect their severity. In this study, we determined that another age-dependent phenotype, ectopic synapse formation, is also accelerated in the A/J retina compared to the B6 retina. Through genetic mapping utilizing recombinant inbred strains, we identified quantitative trait loci (QTLs) on chromosome 7 and 19 that contribute to abnormal retinal synapses as well as other age-dependent phenotypes. Using consomic single chromosome substitution lines where a single chromosome is from A/J and the rest of the genome is B6, we investigated the individual effect of each QTL on retinal aging phenotypes. We observed that both QTLs independently contribute to abnormal retinal synapses, reduction in the number of cone cells, and an up-regulation of retinal stress marker, glial fibrillary acidic protein (GFAP). Mice with a single chromosome substitution on chromosome 19 also exhibited an increase in inflammatory cells, which is characteristic of aging and age-related macular degeneration. Thus, we identified QTLs that are independently capable of affecting the severity and progression of age-dependent retinal abnormalities in mice.
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影响因子：
56.9
作者：
Singer, JB;Hill, AE;Nadeau, JH
通讯作者：
Nadeau, JH
DOI：
10.1111/j.1460-9568.2011.07944.x
发表时间：
2012-01
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Hughes S;Pothecary CA;Jagannath A;Foster RG;Hankins MW;Peirson SN
通讯作者：
Peirson SN
影响因子：
3.4
作者：
Goldstein, JA
通讯作者：
Goldstein, JA
影响因子：
3.7
作者：
Fuchs M;Scholz M;Sendelbeck A;Atorf J;Schlegel C;Enz R;Brandstätter JH
通讯作者：
Brandstätter JH
影响因子：
6.2
作者：
BAILEY, DW
通讯作者：
BAILEY, DW