PUBLICATION
Cross-species characterization of the ALS2 gene and analysis of its pattern of expression in development and adulthood
- Authors
- Devon, R.S., Schwab, C., Topp, J.D., Orban, P.C., Yang, Y.Z., Pape, T.D., Helm, J.R., Davidson, T.L., Rogers, D.A., Gros-Louis, F., Rouleau, G., Horazdovsky, B.F., Leavitt, B.R., and Hayden, M.R.
- ID
- ZDB-PUB-080826-46
- Date
- 2005
- Source
- Neurobiology of disease 18(2): 243-257 (Journal)
- Registered Authors
- Keywords
- ALS2, Alsin, ALS2CL, lacZ, Cerebellum, Endosome
- MeSH Terms
-
- Animals
- Molecular Sequence Data
- Rats
- Humans
- Takifugu
- Endosomes/metabolism
- Lac Operon/genetics
- Actin Cytoskeleton/metabolism
- Guanine Nucleotide Exchange Factors/genetics
- Guanine Nucleotide Exchange Factors/metabolism*
- Zebrafish
- Genes, Reporter/genetics
- Neurons/metabolism*
- Nerve Tissue Proteins/genetics
- Sequence Homology, Amino Acid
- Mice
- Sequence Homology, Nucleic Acid
- Anopheles
- Adaptor Proteins, Signal Transducing
- Central Nervous System/embryology*
- Central Nervous System/growth & development*
- Central Nervous System/metabolism
- Mice, Inbred C57BL
- Gene Expression Regulation, Developmental/genetics*
- Zebrafish Proteins/genetics
- Drosophila melanogaster
- Pan troglodytes
- Species Specificity
- Cerebellar Cortex/embryology
- Cerebellar Cortex/growth & development
- Cerebellar Cortex/metabolism
- Mice, Transgenic
- Carrier Proteins/genetics
- PubMed
- 15686953 Full text @ Neurobiol. Dis.
Citation
Devon, R.S., Schwab, C., Topp, J.D., Orban, P.C., Yang, Y.Z., Pape, T.D., Helm, J.R., Davidson, T.L., Rogers, D.A., Gros-Louis, F., Rouleau, G., Horazdovsky, B.F., Leavitt, B.R., and Hayden, M.R. (2005) Cross-species characterization of the ALS2 gene and analysis of its pattern of expression in development and adulthood. Neurobiology of disease. 18(2):243-257.
Abstract
Mutations in the ALS2 gene, which encodes alsin, cause autosomal recessive juvenile-onset amyotrophic lateral sclerosis (ALS2) and related conditions. Using both a novel monoclonal antibody and LacZ knock-in mice, we demonstrate that alsin is widely expressed in neurons of the CNS, including the cortex, brain stem and motor neurons of the spinal cord. Interestingly, the highest levels of alsin are found in the molecular layer of the cerebellum, a brain region not previously implicated in ALS2. During development, alsin is expressed by day E9.5, but CNS expression does not become predominant until early postnatal life. At the subcellular level, alsin is tightly associated with endosomal membranes and is likely to be part of a large protein complex that may include the actin cytoskeleton. ALS2 is present in primates, rodents, fish and flies, but not in the nematode worm or yeast, and is more highly conserved than expected among mammals. Additionally, the product of a second, widely expressed gene, ALS2 C-terminal like (ALS2CL), may subserve or modulate some of the functions of alsin as an activator of Rab and Rho GTPases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping