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PMID: 24359958 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Mouse models of PI(3,5)P2 deficiency with impaired lysosome function.

Methods in enzymology ·Vol. 534 ·2014-00-00 ·Pages 245-60

Lenk GM, Meisler MH

Abstract

The endolysosomal system and autophagy are essential components of macromolecular turnover in eukaryotic cells. The low-abundance signaling lipid PI(3,5)P2 is a key regulator of this pathway. Analysis of mouse models with defects in PI(3,5)P2 biosynthesis has revealed the unique dependence of the mammalian nervous system on this signaling pathway. This insight led to the discovery of the molecular basis for several human neurological disorders, including Charcot-Marie-Tooth disease and Yunis-Varon syndrome. Spontaneous mutants, conditional knockouts, transgenic lines, and gene-trap alleles of Fig4, Vac14, and Pikfyve (Fab1) in the mouse have provided novel information regarding the role of PI(3,5)P2in vivo. This review summarizes what has been learned from mouse models and highlights the utility of manipulating complex signaling pathways in vivo.

Keywords
Autophagy Conditional FAB1 FIG4 Lysosome Neurological mutant PIKFYVE Transgenic VAC14
MeSH Terms
Alleles Animals Astrocytes/metabolism,pathology Disease Models, Animal Female Flavoproteins/genetics,metabolism Gene Knockout Techniques Hereditary Sensory and Motor Neuropathy/genetics,metabolism,pathology Heterozygote Homozygote Humans Male Mice Mice, Transgenic Neurons/metabolism,pathology Phosphatidylinositol 3-Kinases/deficiency,genetics Phosphatidylinositol Phosphates/deficiency Phosphoinositide Phosphatases Protein Tyrosine Phosphatases, Non-Receptor/deficiency,genetics
Chemicals
Flavoproteins Phosphatidylinositol Phosphates phosphatidylinositol 3,5-diphosphate Phosphatidylinositol 3-Kinases Pikfyve protein, mouse Fig4 protein, mouse Phosphoinositide Phosphatases Mtmr2 protein, mouse Protein Tyrosine Phosphatases, Non-Receptor
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lenk Guy M
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Meisler Miriam H
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: meislerm@umich.edu.
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31 references, click to expand
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Article Info
Journal
Methods in enzymology
Abbr.
Methods Enzymol
ISSN
1557-7988
DOI
10.1016/B978-0-12-397926-1.00014-7
Email
meislerm@umich.edu
Published
2014-00-00
Pages
245-60
Language
English
Region
United States
NLM ID
0212271
PMCID
PMC4059992
Subset
IM
Grants
NIGMS NIH HHS · R01 GM024872 · United States
NCATS NIH HHS · UL1 TR000433 · United States
NIGMS NIH HHS · GM24872 · United States
External Links
PubMed source DOI: 10.1016/B978-0-12-397926-1.00014-7 PMC Full Text
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