Philips Mari-Anne, Lilleväli Kersti, Heinla Indrek, Luuk Hendrik, Hundahl Christian Ansgar, Kongi Karina, Vanaveski Taavi, Tekko Triin, Innos Jürgen, Vasar Eero
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia,
Brain Struct Funct. 2015;220(3):1381-93. doi: 10.1007/s00429-014-0732-x. Epub 2014 Mar 15.
Limbic system-associated membrane protein (LSAMP) is a neural cell adhesion molecule involved in neurite formation and outgrowth. The purpose of the present study was to characterize the distribution of alternatively transcribed Lsamp isoforms in the mouse brain and its implications on the regulation of behavior. Limbic system-associated membrane protein 1b transcript was visualized by using a mouse strain expressing beta-galactosidase under the control of Lsamp 1b promoter. The distribution of Lsamp 1a transcript and summarized expression of the Lsamp transcripts was investigated by non-radioactive in situ RNA hybridization analysis. Cross-validation was performed by using radioactive in situ hybridization with oligonucleotide probes. Quantitative RT-PCR was used to study correlations between the expression of Lsamp isoforms and behavioral parameters. The expression pattern of two promoters differs remarkably from the developmental initiation at embryonic day 12.5. Limbic system-associated membrane protein 1a promoter is active in "classic" limbic structures where the hippocampus and amygdaloid area display the highest expression. Promoter 1b is mostly active in the thalamic sensory nuclei and cortical sensory areas, but also in areas that regulate stress and arousal. Higher levels of Lsamp 1a transcript had significant correlations with all of the measures indicating higher trait anxiety in the elevated plus-maze test. Limbic system-associated membrane protein transcript levels in the hippocampus and ventral striatum correlated with behavioral parameters in the social interaction test. The data are in line with decreased anxiety and alterations in social behavior in Lsamp-deficient mice. We propose that Lsamp is involved in emotional and social operating systems by complex regulation of two alternative promoters.
边缘系统相关膜蛋白（LSAMP）是一种参与神经突形成和生长的神经细胞粘附分子。本研究的目的是表征小鼠脑中可变转录的Lsamp亚型的分布及其对行为调节的影响。通过使用在Lsamp 1b启动子控制下表达β-半乳糖苷酶的小鼠品系来观察边缘系统相关膜蛋白1b转录本。通过非放射性原位RNA杂交分析研究Lsamp 1a转录本的分布和Lsamp转录本的汇总表达。使用与寡核苷酸探针的放射性原位杂交进行交叉验证。定量RT-PCR用于研究Lsamp亚型表达与行为参数之间的相关性。两种启动子的表达模式在胚胎第12.5天的发育起始时显著不同。边缘系统相关膜蛋白1a启动子在“经典”边缘结构中活跃，其中海马体和杏仁核区域表达最高。启动子1b主要在丘脑感觉核和皮质感觉区域活跃，但也在调节应激和觉醒的区域活跃。在高架十字迷宫试验中，较高水平的Lsamp 1a转录本与所有表明特质焦虑较高的指标显著相关。海马体和腹侧纹状体中的边缘系统相关膜蛋白转录水平与社交互动试验中的行为参数相关。这些数据与Lsamp缺陷小鼠的焦虑降低和社交行为改变一致。我们提出，Lsamp通过对两个可变启动子的复杂调节参与情绪和社交操作系统。
