Absence of TI-VAMP/Vamp7 leads to increased anxiety in mice.
Vesicular (v)- and target (t)-SNARE proteins assemble in SNARE complex to mediate membrane fusion. Tetanus neurotoxin-insensitive vesicular-associated membrane protein (TI-VAMP/VAMP7), a vesicular SNARE expressed in several cell types including neurons, was previously shown to play a major role in exocytosis involved in neurite growth in cultured neurons. Here we generated a complete constitutive knock-out by deleting the exon 3 of Vamp7. Loss of TI-VAMP expression did not lead to any striking developmental or neurological defect. Knock-out mice displayed decreased brain weight and increased third ventricle volume. Axon growth appeared normal in cultured knock-out neurons. Behavioral characterization unraveled that TI-VAMP knock-out was associated with increased anxiety. Our results thus suggest compensatory mechanisms allowing the TI-VAMP knock-out mice to fulfill major developmental processes. The phenotypic traits unraveled here further indicate an unexpected role of TI-VAMP-mediated vesicular traffic in anxiety and suggest a role for TI-VAMP in higher brain functions.
Program in Development and Neurobiology, Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
Lydia
L
Danglot
Kathleen
K
Zylbersztejn
Maja
M
Petkovic
Maxime
M
Gauberti
Hamid
H
Meziane
Roy
R
Combe
Marie-France
MF
Champy
Marie-Christine
MC
Birling
Guillaume
G
Pavlovic
Jean-Charles
JC
Bizot
Fabrice
F
Trovero
Floriana
F
Della Ragione
Véronique
V
Proux-Gillardeaux
Tania
T
Sorg
Denis
D
Vivien
Maurizio
M
D'Esposito
Thierry
T
Galli
D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000235:genetics* / Q000523:psychology; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D008297:Male; D008666:Metalloendopeptidases / Q000008:administration & dosage; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050683:R-SNARE Proteins / Q000172:deficiency* / Q000235:genetics*; D011817:Rabbits; D013744:Tetanus Toxin / Q000008:administration & dosage
D050683:R-SNARE Proteins; C496927:Sybl1 protein, mouse; D013744:Tetanus Toxin; C035979:tetanospasmin; D008666:Metalloendopeptidases