A rat model of a focal mosaic expression of PCDH19 replicates human brain developmental abnormalities and behaviours.
A rat model of a focal mosaic expression of PCDH19 replicates human brain developmental abnormalities and behaviours.
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PCDH19局灶性镶嵌表达的大鼠模型复制了人脑发育异常和行为。
DOI：
10.1093/braincomms/fcac091
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发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
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作者：
原钙粘蛋白19基因相关癫痫或原钙粘蛋白19聚集性癫痫是一种以不同程度的精神（包括自闭症相关）、感觉和认知障碍为特征的婴儿癫痫综合征。原钙粘蛋白19聚集性癫痫是由x -连锁原钙粘蛋白19功能丧失引起的。由于随机x染色体失活，原钙粘蛋白19聚集性癫痫影响的女性呈现健康和原钙粘蛋白19突变细胞的马赛克群体。不幸的是，到目前为止，还没有一种小鼠模型能够完全再现原钙粘蛋白19聚集性癫痫患者的脑组织和行为缺陷。因此，寻求对这种疾病的正确认识和未来可能的治疗受到阻碍。通过在大鼠子宫内电穿孔诱导原钙粘蛋白19表达的局部嵌合，我们发现特定脑区域的原钙粘蛋白19信号传导与神经元迁移、热致癫痫发作、与自闭症和认知功能相关的核心/共病行为有关。Cwetsch等人报道了子宫内电穿孔诱导PCDH19下调局灶性脑嵌合的大鼠模型，旨在模仿PCDH19- ce人的x连锁遗传模式。局部嵌合的Pcdh19下调可导致大脑发育缺陷、热致癫痫发作、自闭症相关行为和认知能力下降。
Protocadherin 19 gene-related epilepsy or protocadherin 19 clustering epilepsy is an infantile-onset epilepsy syndrome characterized by psychiatric (including autism-related), sensory, and cognitive impairment of varying degrees. Protocadherin 19 clustering epilepsy is caused by X-linked protocadherin 19 protein loss of function. Due to random X-chromosome inactivation, protocadherin 19 clustering epilepsy-affected females present a mosaic population of healthy and protocadherin 19-mutant cells. Unfortunately, to date, no current mouse model can fully recapitulate both the brain histological and behavioural deficits present in people with protocadherin 19 clustering epilepsy. Thus, the search for a proper understanding of the disease and possible future treatment is hampered. By inducing a focal mosaicism of protocadherin 19 expression using in utero electroporation in rats, we found here that protocadherin 19 signalling in specific brain areas is implicated in neuronal migration, heat-induced epileptic seizures, core/comorbid behaviours related to autism and cognitive function. Cwetsch et al. report a rat model of focal brain mosaicism of PCDH19 downregulation induced by in utero electroporation, aimed at mimicking the X-linked inheritance pattern of PCDH19-CE people. A local mosaic of Pcdh19 downregulation resulted in brain development deficits, heat-induced epileptic seizures, autism-related behaviors, and reduced cognitive performance.
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影响因子：
4.6
作者：
Eissa N;Jayaprakash P;Azimullah S;Ojha SK;Al-Houqani M;Jalal FY;Łażewska D;Kieć-Kononowicz K;Sadek B
通讯作者：
Sadek B
影响因子：
3.5
作者：
Bassani S;Cwetsch AW;Gerosa L;Serratto GM;Folci A;Hall IF;Mazzanti M;Cancedda L;Passafaro M
通讯作者：
Passafaro M
影响因子：
3.9
作者：
Depienne, Christel;Trouillard, Oriane;Bouteiller, Delphine;Gourfinkel-An, Isabelle;Poirier, Karine;Rivier, Francois;Berquin, Patrick;Nabbout, Rima;Chaigne, Denys;Steschenko, Dominique;Gautier, Agnes;Hoffman-Zacharska, Dorota;Lannuzel, Annie;Lackmy-Port-Lis, Marilyn;Maurey, Helene;Dusser, Anne;Bru, Marie;Gilbert-Dussardier, Brigitte;Roubertie, Agathe;Kaminska, Anna;Whalen, Sandra;Mignot, Cyril;Baulac, Stephanie;Lesca, Gaetan;Arzimanoglou, Alexis;LeGuern, Eric
通讯作者：
LeGuern, Eric
影响因子：
--
作者：
Clarke C
通讯作者：
Clarke C
DOI：
10.1037/h0077458
发表时间：
1978-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
ALBERTS, JR
通讯作者：
ALBERTS, JR