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

Biochem Biophys Res Commun. 2012 Oct 5;426(4):533-8. doi: 10.1016/j.bbrc.2012.08.122. Epub 2012 Sep 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / abnormalities
  • Brain / metabolism
  • Cell Lineage*
  • Germ Cells / metabolism
  • 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
  • Phenotype
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • beta-Galactosidase / biosynthesis


  • Intermediate Filament Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • RNA, Messenger
  • Vesicular Transport Proteins
  • girdin protein, mouse
  • Insulin-Like Growth Factor I
  • beta-Galactosidase