Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2.
Although abnormal processing of amyloid precursor protein (APP) leads to early onset of Alzheimer's disease, the normal function of this protein is poorly understood. APP is widely expressed in axons, dendrites, and synapses in both central and peripheral nervous systems. Mice homozygous for APP or its homologue APP-like protein 2 (APLP2) null mutation (KO) are viable, but double mutants for APP and APLP2 deletions (DKO) are early postnatal lethal. To investigate the role of APP in synapse development, we compared the ultrastructure of submandibular ganglion synapses between DKO and littermate APLP2 KO mice at birth. Using serial electron microscopy, we found that the size of presynaptic boutons and the number of active zones per bouton were comparable in both strains of animals. However, the synaptic vesicle density, active zone size, and docked vesicle number per active zone were significantly reduced in DKO compared to those in APLP2 KO. These results indicate that the APP family of proteins plays an important role in regulating the formation and function of inter-neuronal synapses.
Yang
Guang
G
State Key Lab of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China.
Gong
Yan-Dao
YD
Gong
Kai
K
Jiang
Wu-Ling
WL
Kwon
Elaine
E
Wang
Pei
P
Zheng
Hui
H
Zhang
Xiu-Fang
XF
Gan
Wen-Biao
WB
Zhao
Nan-Ming
NM
D016564:Amyloid beta-Protein Precursor / Q000172:deficiency*; D000818:Animals; D021621:Imaging, Three-Dimensional / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000473:pathology* / Q000648:ultrastructure
D016564:Amyloid beta-Protein Precursor; C492952:Aplp2 protein, mouse; D008562:Membrane Glycoproteins