title: Deletion of the amyloid precursor-like protein 2 (APLP2) does not affect hippocampal neuron morphology or function.
abstract: Amyloid precursor protein (APP), the parent molecule to amyloid β peptide, 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 β 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.
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Brea
authors.initials: B
authors.lastname: Midthune
authors.forename: Sheue-Houy
authors.initials: SH
authors.lastname: Tyan
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Walsh
authors.forename: Floyd
authors.initials: F
authors.lastname: Sarsoza
authors.forename: Simone
authors.initials: S
authors.lastname: Eggert
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.forename: Dara L
authors.initials: DL
authors.lastname: Dickstein
authors.forename: Edward H
authors.initials: EH
authors.lastname: Koo
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D048430:Cell Shape; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques
chemical_list: D016564:Amyloid beta-Protein Precursor; C492952:Aplp2 protein, mouse