Deletion of the amyloid precursor-like protein 2 (APLP2) does not affect hippocampal neuron morphology or function

详细信息	查看全文 | 推荐本文 |

• 作者：Brea Midthune^a ; Sheue-Houy Tyan^a ; Jessica J. Walsh^b ; Floyd Sarsoza^a ; Simone Eggert^a ; ¹ ; Patrick R. Hof^b ; Dara L. Dickstein^b ; Edward H. Koo^a ; ^{edkoo@ucsd.edu}
• 关键词：AD ; Alzheimer's disease ; A尾 ; amyloid-beta peptide ; APP ; amyloid precursor protein ; APLP1 ; amyloid precursor-like protein 1 ; APLP2 ; amyloid precursor-like protein 2 ; DIV ; days in vitro ; eGFP ; enhanced green fluorescent protein ; DAPI ; 4&prime ; 6-diamidino-2
• 刊名：Molecular and Cellular Neuroscience
• 出版年：2012
• 期刊代码：173_10447431
• 类别：bio
• 出版时间：April, 2012
• 卷：49
• 期：4
• 页码：448-455
• 文件大小：765 K

摘要

Amyloid precursor protein (APP), the parent molecule to amyloid 尾 飥爌eptide, is part of a larger gene family with two mammalian homologues, amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2). Initial knock-out studies demonstrated that while single APP family gene deletions produced relatively mild phenotypes, deficiency of APLP2 and one other member of the gene family resulted in perinatal lethality, suggesting vital roles masked by functional redundancy of the other homologues. Because of the importance of APP in Alzheimer's disease, the vast majority of studies to date have concentrated on the neuronal functions of APP, leaving limited data on its homologues. APLP2 is of particular interest as it contains high sequence homology with APP, is processed similarly, is expressed in overlapping spatial and temporal patterns, and is obligatory for lethality when combined with deficiency of either APLP1 or APP but does not contain the toxic amyloid 尾 sequence. Here we sought to test the role of APLP2 on neuronal structure and function using a combined approach involving in vitro and in vivo techniques in young and aged animals. Surprisingly, we found that unlike APP, APLP2 appears not to be essential for maintenance of dendritic structure, spine density, or synaptic function. Thus, there is clear divergence in the functional redundancy between APP and APLP2.