Integrin β3 in forebrain Emx1-expressing cells regulates repetitive self-grooming and sociability in mice.
Integrin β3 in forebrain Emx1-expressing cells regulates repetitive self-grooming and sociability in mice.
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前脑Emx 1表达细胞中的整合素β3调节小鼠的重复自我梳理和社交能力
DOI：
10.1186/s12868-022-00691-2
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发表时间：
2022-03-05
期刊：
影响因子：
2.4
通讯作者：
Vidal GS
中科院分区：
文献类型：
--
作者：
Lopuch AJ;Swinehart BD;Widener EL;Holley ZL;Bland KM;Handwerk CJ;Brett CA;Cook HN;Kalinowski AR;Rodriguez HV;Song MI;Vidal GS
自闭症谱系障碍（ASD）的特征是重复的行为，沟通障碍和整体受损的社会互动。在所有整合素亚基突变中，整合素β3（Itgb 3）突变可能与ASD最密切相关。整合素β3是树突和突触的正常结构可塑性所必需的，特别是在兴奋性皮质和海马回路中。然而，Itgb 3功能在前脑中的行为后果尚未评估。我们测试了这一假设，即ASD中典型的异常行为，如自我修饰和社交行为，在雄性和雌性小鼠的前脑回路中被有条件的Itgb 3功能丧失所破坏。我们产生了男性和女性条件性基因敲除（cKO）和条件性杂合子（cHET）Itgb 3兴奋性神经元和神经胶质细胞，来自Emx 1表达前脑细胞在发展过程中。我们使用几种不同的测定来确定与雄性和雌性野生型（WT）小鼠相比，雄性和雌性cKO和cHET小鼠是否具有重复的自我梳理行为、焦虑样行为、异常运动、强迫样行为或异常社会行为。我们的研究结果表明，只有自我梳理和社交性在cKO中改变，而不是cHET或WT小鼠，这表明Itgb 3在前脑Emx 1表达细胞中是正常重复自我梳理和社交行为所必需的。此外，在cKO（而不是cHET或WT）中，我们观察到性别和自我修饰环境的交互作用以及性别和社交测试室的交互作用。虽然这项研究证明了前脑Itgb 3在特定的重复和社会行为中的作用，但无法确定前脑Itgb 3是否是偏好社会新奇所必需的，cHET是否在重复的自我修饰和社会行为方面是单倍不足的，或者在cKO受影响的行为中性别和环境/腔室的相互作用效应的性质。总之，这些发现加强了Itgb 3在塑造与自闭症谱系障碍的内表型相关的前脑回路中具有特定作用的观点。在线版本包含补充材料，可通过10.1186/s12868-022-00691-2获得。
Autism spectrum disorder (ASD) is characterized by repetitive behaviors, deficits in communication, and overall impaired social interaction. Of all the integrin subunit mutations, mutations in integrin β3 (Itgb3) may be the most closely associated with ASD. Integrin β3 is required for normal structural plasticity of dendrites and synapses specifically in excitatory cortical and hippocampal circuitry. However, the behavioral consequences of Itgb3 function in the forebrain have not been assessed. We tested the hypothesis that behaviors that are typically abnormal in ASD—such as self-grooming and sociability behaviors—are disrupted with conditional Itgb3 loss of function in forebrain circuitry in male and female mice. We generated male and female conditional knockouts (cKO) and conditional heterozygotes (cHET) of Itgb3 in excitatory neurons and glia that were derived from Emx1-expressing forebrain cells during development. We used several different assays to determine whether male and female cKO and cHET mice have repetitive self-grooming behaviors, anxiety-like behaviors, abnormal locomotion, compulsive-like behaviors, or abnormal social behaviors, when compared to male and female wildtype (WT) mice. Our findings indicate that only self-grooming and sociability are altered in cKO, but not cHET or WT mice, suggesting that Itgb3 is specifically required in forebrain Emx1-expressing cells for normal repetitive self-grooming and social behaviors. Furthermore, in cKO (but not cHET or WT), we observed an interaction effect for sex and self-grooming environment and an interaction effect for sex and sociability test chamber. While this study demonstrated a role for forebrain Itgb3 in specific repetitive and social behaviors, it was unable to determine whether forebrain Itgb3 is required for a preference for social novelty, whether cHET are haploinsufficient with respect to repetitive self-grooming and social behaviors, or the nature of the interaction effect for sex and environment/chamber in affected behaviors of cKO. Together, these findings strengthen the idea that Itgb3 has a specific role in shaping forebrain circuitry that is relevant to endophenotypes of autism spectrum disorder. The online version contains supplementary material available at 10.1186/s12868-022-00691-2.
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影响因子：
10.6
作者：
McCarthy MM;Wright CL
通讯作者：
Wright CL
DOI：
10.1002/ajmg.b.31003
发表时间：
2010-03-05
影响因子：
2.8
作者：
Ma, D. Q.;Rabionet, R.;Konidari, I.;Jaworski, J.;Cukier, H. N.;Wright, H. H.;Abramson, R. K.;Gilbert, J. R.;Cuccaro, M. L.;Pericak-Vance, M. A.;Martin, E. R.
通讯作者：
Martin, E. R.
影响因子：
15.9
作者：
Hodivala-Dilke, KM;McHugh, KP;Hynes, RO
通讯作者：
Hynes, RO
影响因子：
64.8
作者：
Chavis, P;Westbrook, G
通讯作者：
Westbrook, G
影响因子：
2.5
作者：
McFarlane, H. G.;Kusek, G. K.;Crawley, J. N.
通讯作者：
Crawley, J. N.