title: Enhanced fear expression in Spir-1 actin organizer mutant mice.
abstract: Spir proteins nucleate actin filaments at vesicle membranes and facilitate intracellular transport processes. The mammalian genome encodes two Spir proteins, namely Spir-1 and Spir-2. While the mouse spir-2 gene has a rather broad expression pattern, high levels of spir-1 expression are restricted to the nervous system, oocytes, and testis. Spir-1 mutant mice generated by a gene trap method have been employed to address Spir-1 function during mouse development and in adult mouse tissues, with a specific emphasis on viability, reproduction, and the nervous system. The gene trap cassette disrupts Spir-1 expression between the N-terminal KIND domain and the WH2 domain cluster. Spir-1 mutant mice are viable and were born in a Mendelian ratio. In accordance with the redundant function of Spir-1 and Spir-2 in oocyte maturation, spir-1 mutant mice are fertile. The overall brain anatomy of spir-1 mutant mice is not altered and visual and motor functions of the mice remain normal. Microscopic analysis shows a slight reduction in the number of dendritic spines on cortical neurons. Detailed behavioral studies of the spir-1 mutant mice, however, unveiled a very specific and highly significant phenotype in terms of fear learning in male mice. In contextual and cued fear conditioning experiments the male spir-1 mutant mice display increased fear memory when compared to their control littermates. Our data point toward a particular function of the vesicle associated Spir-1 actin organizer in neuronal circuits determining fear behavior.
authors.affiliation: University Hospital Regensburg, Department of Neurology, Molecular Cell Biology Laboratory, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pleiser
authors.affiliation: European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Via Ramarini 32, 00015 Monterotondo, Italy; Campus Vienna Biocenter, CSF - Campus Science Support Facilities GmbH, Dr. Bohr-Gasse 7, 1020 Vienna, Austria.
authors.forename: Mumna Al
authors.initials: MA
authors.lastname: Banchaabouchi
authors.affiliation: University Hospital Regensburg, Department of Neurology, Molecular Cell Biology Laboratory, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Samol-Wolf
authors.affiliation: European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Via Ramarini 32, 00015 Monterotondo, Italy.
authors.forename: Dominika
authors.initials: D
authors.lastname: Farley
authors.affiliation: University Hospital Regensburg, Department of Neurology, Molecular Cell Biology Laboratory, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welz
authors.affiliation: University Hospital Regensburg, Department of Neurology, Molecular Cell Biology Laboratory, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Joel
authors.initials: J
authors.lastname: Wellbourne-Wood
authors.affiliation: University Hospital Regensburg, Department of Neurology, Molecular Cell Biology Laboratory, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Gehring
authors.affiliation: Hannover Medical School, Institute for Biophysical Chemistry, Carl-Neuberg Straße 1, 30625 Hannover, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Linkner
authors.affiliation: Hannover Medical School, Institute for Biophysical Chemistry, Carl-Neuberg Straße 1, 30625 Hannover, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Faix
authors.affiliation: Regensburg University Hospital, Department of Neuropathology, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Riemenschneider
authors.affiliation: University Hospital Regensburg, Department of Neurology, Molecular Cell Biology Laboratory, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Dietrich
authors.affiliation: University Hospital Regensburg, Department of Neurology, Molecular Cell Biology Laboratory, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. Electronic address: eugen.kerkhoff@klinik.uni-regensburg.de.
authors.forename: Eugen
authors.initials: E
authors.lastname: Kerkhoff
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D003214:Conditioning, Classical; D003712:Dendrites / Q000378:metabolism; D049229:Dendritic Spines / Q000648:ultrastructure; D005239:Fear / Q000523:psychology*; D005260:Female; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D022161:Transport Vesicles / Q000235:genetics / Q000378:metabolism; D014796:Visual Perception
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C556674:Spir-2 protein, mouse; C493004:Spire1 protein, mouse
keywords: Actin; Emotional learning; Fear conditioning; Fmn-2; Formin; Mouse genetics; Nervous system; Spir-1