Similar phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage

► Girdin is expressed throughout the nervous system including brain and spinal cord. ► We generated nestin lineage-specific Girdin conditional knockout (cKO) mice. ► Loss of Girdin from the nestin lineage produces abnormalities in the brain. ► The phenotype of Girdin cKO mice was almost identical to...

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Published in:	Biochemical and biophysical research communications Vol. 426; no. 4; pp. 533 - 538
Main Authors:	Asai, Masato, Asai, Naoya, Murata, Ayana, Yokota, Hirofumi, Ohmori, Kenji, Mii, Shinji, Enomoto, Atsushi, Murakumo, Yoshiki, Takahashi, Masahide
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 05-10-2012
Subjects:	Amino Acid Sequence Animals beta-Galactosidase - biosynthesis Brain - abnormalities Brain - metabolism Cell Lineage Germ Cells - metabolism Girdin Granule cell dispersion Hypothalamus - abnormalities Hypothalamus - metabolism Insulin-Like Growth Factor I - genetics Intermediate Filament Proteins - genetics Mice Mice, Knockout Microfilament Proteins - genetics Microfilament Proteins - metabolism Molecular Sequence Data Nerve Tissue Proteins - genetics Nestin Neuronal migration Phenotype RMS RNA, Messenger - analysis RNA, Messenger - biosynthesis Vesicular Transport Proteins - genetics Vesicular Transport Proteins - metabolism Neuronal migration RMS Granule cell dispersion Nestin Girdin
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Summary:	► Girdin is expressed throughout the nervous system including brain and spinal cord. ► We generated nestin lineage-specific Girdin conditional knockout (cKO) mice. ► Loss of Girdin from the nestin lineage produces abnormalities in the brain. ► The phenotype of Girdin cKO mice was almost identical to non-conditional KO mice. Girdin is an Akt substrate and actin-binding protein. Mice with germ-line deletions of Girdin (a non-conditional knockout, (ncKO)) exhibit complete postnatal lethality accompanied by growth retardation and neuronal cell migration defects, which results in hypoplasia of the olfactory bulb and granule cell dispersion in the dentate gyrus. However, the physiological and molecular abnormalities in Girdin ncKO mice are not fully understood. In this study, we first defined the distribution of Girdin in neonates (P1) and adults (6months or older) using β-galactosidase activity in tissues from ncKO mice. The results indicate that Girdin is expressed throughout the nervous system (brain, spinal cord, enteric and autonomic nervous systems). In addition, β-galactosidase activity was detected in non-neural tissues, particularly in tissues with high tensile force, such as tendons, heart valves, and skeletal muscle. In order to identify the cellular population where the Girdin ncKO phenotype originates, newly generated Girdin flox mice were crossed with nestin promoter-driven Cre transgenic mice to obtain Girdin conditional knockout (cKO) mice. The phenotype of Girdin cKO mice was almost identical to ncKO mice, including postnatal lethality, growth retardation and decreased neuronal migration. Our findings indicate that loss of Girdin in the nestin cell lineage underlies the phenotype of Girdin ncKO mice.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-291X 1090-2104
DOI:	10.1016/j.bbrc.2012.08.122