Sex-specific behavioral traits in the Brd2 mouse model of juvenile myoclonic epilepsy.
Sex-specific behavioral traits in the Brd2 mouse model of juvenile myoclonic epilepsy.
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DOI：
10.1111/gbb.12160
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Velíšek L
中科院分区：
文献类型：
--
作者：
Chachua T;Goletiani C;Maglakelidze G;Sidyelyeva G;Daniel M;Morris E;Miller J;Shang E;Wolgemuth DJ;Greenberg DA;Velíšková J;Velíšek L
特发性全身性癫痫占人类所有癫痫的约30-35%。布罗莫结构域BRD 2基因已多次与青少年肌阵挛性癫痫亚综合征相关。我们之前的工作确定，Brd 2单倍不足（Brd 2 +/−）的小鼠对激发性癫痫发作的易感性增加，发生自发性癫痫发作，并且直接基底神经节通路以及新皮质和上级丘中的GABA标记物显著减少。在这里，我们测试了雄性和雌性Brd 2 +/−和野生型同窝小鼠的一系列行为测试（旷场，管优势测试，高架十字迷宫，莫里斯水迷宫和巴恩斯迷宫），以确定是否Brd 2单倍不足与人类行为模式，所谓的青少年肌阵挛性癫痫人格。Brd 2 +/−女性（而非男性）持续表现出焦虑减少。此外，与野生型相比，我们在Brd 2 +/−小鼠中发现了一个非常显著的显性特征（攻击性），在雌性中更为明显。Brd 2 +/−小鼠在空间学习和记忆测试中与野生型小鼠没有差异。与野生型同窝仔相比，我们发现基底外侧杏仁核中GABA神经元的数量减少，这与攻击行为的增加一致。我们的研究结果表明，Brd 2 +/−单倍不足小鼠没有表现出认知障碍，但具有与青少年肌阵挛性癫痫患者相似的行为特征（鲁莽，攻击）。这表明BRD 2基因直接影响青少年肌阵挛性癫痫的许多特征，或者它控制个体表型的上游调节因子。
Idiopathic generalized epilepsy represents about 30–35% of all epilepsies in humans. The bromodomain BRD2 gene has been repeatedly associated with the subsyndrome of juvenile myoclonic epilepsy. Our previous work determined that mice haploinsufficient in Brd2 (Brd2+/−) have increased susceptibility to provoked seizures, develop spontaneous seizures and have significantly decreased GABA markers in the direct basal ganglia pathway as well as in the neocortex and superior colliculus. Here we tested male and female Brd2+/− and wild type littermate mice in a battery of behavioral tests (open field, tube dominance test, elevated plus maze, Morris water maze and Barnes maze) to identify whether Brd2 haploinsufficiency is associated with the human behavioral patterns, so-called juvenile myoclonic epilepsy personality. Brd2+/− females but not males consistently displayed decreased anxiety. Further, we found a highly significant dominance trait (aggression) in the Brd2+/− mice compared to the wild type, more pronounced in females. Brd2+/− mice of either sex did not differ from wild type mice in spatial learning and memory tests. Compared to wild type littermates, we found decreased numbers GABA neurons in the basolateral amygdala, which is consistent with the increase in aggressive behavior. Our results indicate that Brd2+/− haploinsufficient mice show no cognitive impairment but have behavioral traits similar to those found in patients with juvenile myoclonic epilepsy (recklessness, aggression). This suggests that either the BRD2 gene is directly responsible for influencing many traits of juvenile myoclonic epilepsy or it controls upstream regulators of individual phenotypes.
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DOI：
10.1111/j.1601-183x.2009.00476.x
发表时间：
2009-06
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Gangitano D;Salas R;Teng Y;Perez E;De Biasi M
通讯作者：
De Biasi M
影响因子：
3.4
作者：
Johns, Josephine M.;McMurray, Matthew S.;Joyner, Paul W.;Jarrett, Thomas M.;Williams, Sarah K.;Cox, Elizabeth T.;Black, Mitchell A.;Middleton, Christopher L.;Walker, Cheryl H.
通讯作者：
Walker, Cheryl H.
影响因子：
17.1
作者：
Goldstein LE;Fisher AM;Tagge CA;Zhang XL;Velisek L;Sullivan JA;Upreti C;Kracht JM;Ericsson M;Wojnarowicz MW;Goletiani CJ;Maglakelidze GM;Casey N;Moncaster JA;Minaeva O;Moir RD;Nowinski CJ;Stern RA;Cantu RC;Geiling J;Blusztajn JK;Wolozin BL;Ikezu T;Stein TD;Budson AE;Kowall NW;Chargin D;Sharon A;Saman S;Hall GF;Moss WC;Cleveland RO;Tanzi RE;Stanton PK;McKee AC
通讯作者：
McKee AC
影响因子：
8.2
作者：
Choleris, E;Thomas, AW;Prato, FS
通讯作者：
Prato, FS
影响因子：
9.8
作者：
Greenberg, DA;Durner, M;Dicker, E
通讯作者：
Dicker, E