PMID- 23467909
OWN - NLM
STAT- MEDLINE
DCOM- 20140211
LR  - 20161212
IS  - 1699-5848 (Electronic)
IS  - 0213-3911 (Linking)
VI  - 28
IP  - 8
DP  - 2013 Aug
TI  - Mouse models of human INAD by Pla2g6 deficiency.
PG  - 965-9
LID - 10.14670/HH-28.965 [doi]
AB  - Infantile neuroaxonal dystrophy (INAD) is a severe neurodegenerative disease 
      characterized by its early onset. PLA2G6, which encodes a phospholipase A2, 
      iPLA(2)beta, has been identified as a causative gene of INAD. iPLA(2)beta has been shown to 
      be involved in various physiological and pathological processes, including 
      immunity, cell death, and cell membrane homeostasis. Gene targeted mice with a 
      null mutation of Pla2g6 develop the INAD phenotype as late as approximately 1 to 
      2 years after birth. Recently, another INAD mouse model, Pla2g6-INAD mice line, 
      has been established. The Pla2g6-INAD mice bear a point mutation in the ankyrin 
      repeat domain of Pla2g6 generated by N-ethyl-N-nitrosourea mutagenesis. These 
      mutant mice develop severe motor dysfunction and hematopoietic abnormality in a 
      manner following Mendelian law. The mice showed the abnormal gait and poor 
      performance as early as 7 to 8 weeks of age, detected by hanging grip test. 
      Neuropathological examination revealed widespread formation of spheroids 
      containing tubulovesicular membranes similar to human INAD. Molecular and 
      biochemical analysis revealed that the mutant mice expressed Pla2g6 mRNA and 
      protein, but the mutated Pla2g6 protein had no glycerophospholipid-catalyzing 
      enzyme activity. When analyzed the offspring which bear Pla2g6 knockout allele 
      and Pla2g6-INAD allele, abnormal gait appeared slightly later than Pla2g6-INAD 
      homozygotes but with earlier onset than the Pla2g6 knockout homozygotes. This 
      result suggests that mutant Pla2g6 protein contributes to early onset of INAD 
      symptoms in the absence of intact Pla2g6 protein. The analysis of various INAD 
      mouse models may help to understand the pathogenesis of neurodegenerative 
      diseases, including INAD.
FAU - Wada, Haruka
AU  - Wada H
AD  - Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, 
      Sapporo, Japan.
FAU - Kojo, Satoshi
AU  - Kojo S
FAU - Seino, Ken-ichiro
AU  - Seino K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130307
PL  - Spain
TA  - Histol Histopathol
JT  - Histology and histopathology
JID - 8609357
RN  - EC 3.1.1.4 (Group VI Phospholipases A2)
RN  - EC 3.1.1.4 (PLA2G6 protein, human)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - EC 3.1.1.4 (Pla2g6 protein, mouse)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Disease Models, Animal
MH  - Group VI Phospholipases A2/deficiency/*genetics
MH  - Hematopoiesis/genetics
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Mutagenesis, Site-Directed
MH  - Mutation
MH  - Neuroaxonal Dystrophies/*genetics/metabolism
MH  - Neurodegenerative Diseases/metabolism
MH  - Phospholipases A2/metabolism
MH  - Point Mutation
EDAT- 2013/03/08 06:00
MHDA- 2014/02/12 06:00
CRDT- 2013/03/08 06:00
PHST- 2013/03/08 06:00 [entrez]
PHST- 2013/03/08 06:00 [pubmed]
PHST- 2014/02/12 06:00 [medline]
AID - HH-11-309 [pii]
AID - 10.14670/HH-28.965 [doi]
PST - ppublish
SO  - Histol Histopathol. 2013 Aug;28(8):965-9. doi: 10.14670/HH-28.965. Epub 2013 Mar 
      7.