Induced chromosome deletions cause hypersociability and other features of Williams-Beuren syndrome in mice.
Induced chromosome deletions cause hypersociability and other features of Williams-Beuren syndrome in mice.
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DOI：
10.1002/emmm.200900003
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发表时间：
2009-04
影响因子：
11.1
通讯作者：
Francke, Uta
中科院分区：
文献类型：
--
作者：
Li, Hong Hua;Roy, Madhuri;Kuscuoglu, Unsal;Spencer, Corinne M.;Halm, Birgit;Harrison, Katharine C.;Bayle, Joseph H.;Splendore, Alessandra;Ding, Feng;Meltzer, Leslie A.;Wright, Elena;Paylor, Richard;Deisseroth, Karl;Francke, Uta
神经发育障碍 Williams-Beuren 综合征是由人类染色体 7q11.23 上包含 25 个基因的约 1.5 Mb 自发缺失引起的。为了从功能上剖析缺失并识别剂量敏感基因，我们在小鼠染色体 5G2 上创建了两个保守同线区域的半缺失。近端缺失 (PD) 小鼠缺乏 Limk1 的 Gtf2i，远端缺失 (DD) 小鼠缺乏 Limk1 至 Fkbp6，而双杂合子 (D/P) 模型则完全人类缺失。大脑中的基因转录水平通常与基因剂量一致。社交能力和听觉惊吓反应的增强与 PD 相关，而认知缺陷则与 DD 相关。 PD和D/P男性均生长迟缓，而DD和D/P男性的头骨较短，大脑较小。在 PD 和 D/P 中，侧脑室 (LV) 体积减小，体感皮层中的神经元细胞密度增加。 D/P 中运动技能受损最严重。这些部分缺失小鼠共同复制了人类疾病的关键方面，并用于识别导致复杂行为和行为障碍的神经基础的基因和基因网络。
The neurodevelopmental disorder Williams–Beuren syndrome is caused by spontaneous ∼1.5 Mb deletions comprising 25 genes on human chromosome 7q11.23. To functionally dissect the deletion and identify dosage-sensitive genes, we created two half-deletions of the conserved syntenic region on mouse chromosome 5G2. Proximal deletion (PD) mice lack Gtf2i to Limk1, distal deletion (DD) mice lack Limk1 to Fkbp6, and the double heterozygotes (D/P) model the complete human deletion. Gene transcript levels in brain are generally consistent with gene dosage. Increased sociability and acoustic startle response are associated with PD, and cognitive defects with DD. Both PD and D/P males are growth-retarded, while skulls are shortened and brains are smaller in DD and D/P. Lateral ventricle (LV) volumes are reduced, and neuronal cell density in the somatosensory cortex is increased, in PD and D/P. Motor skills are most impaired in D/P. Together, these partial deletion mice replicate crucial aspects of the human disorder and serve to identify genes and gene networks contributing to the neural substrates of complex behaviours and behavioural disorders.
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影响因子：
64.8
作者：
Arron, Joseph R.;Winslow, Monte M.;Crabtree, Gerald R.
通讯作者：
Crabtree, Gerald R.
影响因子：
2.6
作者：
Axelsson, S;Kjær, I;Storhaug, K
通讯作者：
Storhaug, K
影响因子：
3.7
作者：
Ding, Feng;Li, Hong Hua;Zhang, Shengwen;Solomon, Nicola M.;Camper, Sally A.;Cohen, Pinchas;Francke, Uta
通讯作者：
Francke, Uta
影响因子：
9.9
作者：
Gothelf, D;Farber, N;Attias, J
通讯作者：
Attias, J
影响因子：
4
作者：
Aravanis, Alexander M.;Wang, Li-Ping;Deisseroth, Karl
通讯作者：
Deisseroth, Karl