title: Similar phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage.
abstract: 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.
authors.affiliation: Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Masato-a@med.nagoya-u.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Asai
authors.forename: Naoya
authors.initials: N
authors.lastname: Asai
authors.forename: Ayana
authors.initials: A
authors.lastname: Murata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yokota
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohmori
authors.forename: Shinji
authors.initials: S
authors.lastname: Mii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Enomoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakumo
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000378:metabolism; D019070:Cell Lineage; D005854:Germ Cells / Q000378:metabolism; D007031:Hypothalamus / Q000002:abnormalities / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000096:biosynthesis
chemical_list: D007334:Insulin-Like Growth Factor I; D007381:Intermediate Filament Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D001616:beta-Galactosidase; C577485:Nes protein, mouse; C527550:Ccdc88a protein, mouse