Loss of cGMP-dependent protein kinase II alters ultrasonic vocalizations in mice, a model for speech impairment in human microdeletion 4q21 syndrome.
Loss of cGMP-dependent protein kinase II alters ultrasonic vocalizations in mice, a model for speech impairment in human microdeletion 4q21 syndrome.
复制标题
DOI：
10.1016/j.neulet.2021.136048
复制
发表时间：
2021-08-10
影响因子：
2.5
通讯作者：
Kim S
中科院分区：
文献类型：
--
作者：
Tran TM;Sherwood JK;Doolittle MJ;Sathler MF;Hofmann F;Stone-Roy LM;Kim S
染色体 4q21 微缺失会导致一种人类综合症，表现为生长受限、面部畸形、智力低下以及言语缺失或迟缓。 PRKG2 是染色体受影响区域的关键基因之一，它编码 cGMP 依赖性蛋白激酶 II (cGKII)。缺乏 cGKII 的小鼠表现出生长受限以及学习和记忆缺陷，正如人类综合症中所见。然而，这些小鼠的发声障碍尚未确定。人类发声障碍的分子途径尚不完全清楚。在这里，我们采用 cGKII 敲除 (KO) 小鼠作为人类微缺失综合征的模型，以测试发声是否受到 PRKG2 基因缺失的影响。小鼠在社交场合、压力和孤立环境中发出超声波（USV）进行交流。因此，我们记录了超声波发声作为人类语音的模型。我们从巢中分离出生后 5-7 天的幼崽来记录和分析 USV，发现 KO 小鼠的发声相对于野生型和杂合突变小鼠有显着差异。 KO 小鼠发出的叫声较少，持续时间较短，频率较高。由于下丘脑弓状核中的神经元激活对于从巢中隔离后动物 USV 的产生非常重要，因此我们评估了隔离后 KO 幼崽弓状核中的神经元活动。我们发现隔离后 cGKII KO 幼崽的神经元激活显着减少。综上所述，我们的研究表明 cGKII 对于弓状核中的神经元激活很重要，这对新生小鼠中 USV 的产生有显着贡献。我们进一步表明 cGKII KO 小鼠可以成为研究人类 4q21 微缺失综合征病理生理学的有价值的动物模型。
Chromosome 4q21 microdeletion leads to a human syndrome that exhibits restricted growth, facial dysmorphisms, mental retardation, and absent or delayed speech. One of the key genes in the affected region of the chromosome is PRKG2, which encodes cGMP-dependent protein kinase II (cGKII). Mice lacking cGKII exhibit restricted growth and deficits in learning and memory, as seen in the human syndrome. However, vocalization impairments in these mice have not been determined. The molecular pathway underlying vocalization impairment in humans is not fully understood. Here, we employed cGKII knockout (KO) mice as a model for the human microdeletion syndrome to test whether vocalizations are affected by loss of the PRKG2 gene. Mice emit ultrasonic vocalizations (USVs) to communicate in social situations, stress, and isolation. We thus recorded ultrasonic vocalizations as a model for human speech. We isolated postnatal day 5–7 pups from the nest to record and analyze USVs and found significant differences in vocalizations of KO mice relative to wild-type and heterozygous mutant mice. KO mice produced fewer calls that were shorter duration and higher frequency. Because neuronal activation in the arcuate nucleus in the hypothalamus is important for the production of animal USVs following isolation from the nest, we assessed neuronal activity in the arcuate nucleus of KO pups following isolation. We found significant reduction of neuronal activation in cGKII KO pups after isolation. Taken together, our studies indicate that cGKII is important for neuronal activation in the arcuate nucleus, which significantly contributes to the production of USVs in neonatal mice. We further suggest cGKII KO mice can be a valuable animal model to investigate pathophysiology of human microdeletion 4q21 syndrome.
登录
查看更多内容
影响因子：
2.5
作者：
BULLITT, E
通讯作者：
BULLITT, E
影响因子：
10.5
作者：
Chikuda, H;Kugimiya, F;Kawaguchi, H
通讯作者：
Kawaguchi, H
影响因子：
16.2
作者：
Diering GH;Huganir RL
通讯作者：
Huganir RL
DOI：
10.1073/pnas.1417498112
发表时间：
2015-03-10
影响因子：
11.1
作者：
Kim, Seonil;Titcombe, Roseann F.;Ziff, Edward B.
通讯作者：
Ziff, Edward B.
影响因子：
10
作者：
Johnson, Adam F.;Nguyen, Ha T.;Veitia, Reiner A.
通讯作者：
Veitia, Reiner A.