PMID- 10498891
OWN - NLM
STAT- MEDLINE
DCOM- 19991029
LR  - 20121115
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 39
DP  - 1999 Sep 23
TI  - Progressive impairment of kidneys and reproductive organs in mice lacking Rho
      GDIalpha.
PG  - 5373-80
AB  - The Rho small G protein family members regulate various actin
      cytoskeleton-dependent cell functions. The Rho GDI (GDP dissociation inhibitor)
      family, consisting of Rho GDIalpha, -beta, and -gamma, is a regulator that keeps 
      the Rho family members in the cytosol as the GDP-bound inactive form and
      translocates the GDP-bound form from the membranes to the cytosol after the
      GTP-bound form accomplishes their functions. Rho GDIalpha is ubiquitously
      expressed in mouse tissues and shows GDI activity on all the Rho family members
      in vitro. We have generated mice lacking Rho GDIalpha by homologous recombination
      to clarify its in vivo function. Rho GDIalpha -/- mice showed several abnormal
      phenotypes. Firstly, Rho GDIalpha -/- mice were initially viable but developed
      massive proteinuria mimicking nephrotic syndrome, leading to death due to renal
      failure within a year. Histologically, degeneration of tubular epithelial cells
      and dilatation of distal and collecting tubules were readily detected in the
      kidneys. Secondly, Rho GDIalpha -/- male mice were infertile and showed impaired 
      spermatogenesis with vacuolar degeneration of seminiferous tubules in their
      testes. Thirdly, Rho GDIalpha -/- embryos derived from Rho GDIalpha -/- female
      mice were defective in the postimplantation development. In addition, these
      morphological and functional abnormalities showed age-dependent progression.
      These results suggest that the signaling pathways of the Rho family members
      regulated by Rho GDIalpha play important roles in maintaining the structure and
      physiological function of at least kidneys and reproductive systems in adult
      mice.
FAU - Togawa, A
AU  - Togawa A
AD  - Takai Biotimer Project, ERATO, Japan Science and Technology Corporation, c/o JCR 
      Pharmaceuticals Co., Ltd., 2-2-10 Murotani, Nishi-ku, Kobe 651-2241, Japan.
FAU - Miyoshi, J
AU  - Miyoshi J
FAU - Ishizaki, H
AU  - Ishizaki H
FAU - Tanaka, M
AU  - Tanaka M
FAU - Takakura, A
AU  - Takakura A
FAU - Nishioka, H
AU  - Nishioka H
FAU - Yoshida, H
AU  - Yoshida H
FAU - Doi, T
AU  - Doi T
FAU - Mizoguchi, A
AU  - Mizoguchi A
FAU - Matsuura, N
AU  - Matsuura N
FAU - Niho, Y
AU  - Niho Y
FAU - Nishimune, Y
AU  - Nishimune Y
FAU - Nishikawa, S i
AU  - Nishikawa Si
FAU - Takai, Y
AU  - Takai Y
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Arhgdia protein, mouse)
RN  - 0 (Guanine Nucleotide Dissociation Inhibitors)
RN  - 0 (rho Guanine Nucleotide Dissociation Inhibitor alpha)
RN  - 0 (rho-Specific Guanine Nucleotide Dissociation Inhibitors)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Epithelial Cells/pathology
MH  - Female
MH  - Guanine Nucleotide Dissociation Inhibitors/deficiency/genetics/*physiology
MH  - Infertility, Male/etiology/genetics/pathology
MH  - Kidney Tubules/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Nephrotic Syndrome/etiology/genetics
MH  - Renal Insufficiency/*etiology/genetics/metabolism
MH  - Testis/pathology
MH  - rho Guanine Nucleotide Dissociation Inhibitor alpha
MH  - rho-Specific Guanine Nucleotide Dissociation Inhibitors
EDAT- 1999/09/28 00:00
MHDA- 1999/09/28 00:01
CRDT- 1999/09/28 00:00
PHST- 1999/09/28 00:00 [pubmed]
PHST- 1999/09/28 00:01 [medline]
PHST- 1999/09/28 00:00 [entrez]
AID - 10.1038/sj.onc.1202921 [doi]
PST - ppublish
SO  - Oncogene. 1999 Sep 23;18(39):5373-80. doi: 10.1038/sj.onc.1202921.