Enhanced fear expression in Spir-1 actin organizer mutant mice

• Published in: European journal of cell biology Vol. 93; no. 5-6; pp. 225 - 237
• Main Authors: Pleiser, Sandra, Banchaabouchi, Mumna Al, Samol-Wolf, Annette, Farley, Dominika, Welz, Tobias, Wellbourne-Wood, Joel, Gehring, Isabell, Linkner, Jörn, Faix, Jan, Riemenschneider, Markus J., Dietrich, Susanne, Kerkhoff, Eugen
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.05.2014
• Subjects: Actin; Actins - metabolism; Animals; Cells, Cultured; Cerebral Cortex - metabolism; Cerebral Cortex - ultrastructure; Conditioning, Classical; Dendrites - metabolism; Dendritic Spines - ultrastructure; Emotional learning; Fear - psychology; Fear conditioning; Female; Fmn-2; Formin; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Mutant Strains; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Motor Activity; Mouse genetics; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system; Neurons - metabolism; Spir-1; Transport Vesicles - genetics; Transport Vesicles - metabolism; Visual Perception; Fmn-2; Actin; Spir-1; Mouse genetics; Nervous system; Emotional learning; Formin; Fear conditioning
• ISSN: 0171-9335; 1618-1298
• DOI: 10.1016/j.ejcb.2013.11.001

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.