TY - JOUR
T1 - Cross-species characterization of the ALS2 gene and analysis of its pattern of expression in development and adulthood
AU - Devon, Rebecca S.
AU - Schwab, Claudia
AU - Topp, Justin D.
AU - Orban, Paul C.
AU - Yang, Yu Zhou
AU - Pape, Terry D.
AU - Helm, Jeffrey R.
AU - Davidson, Tara Lynne
AU - Rogers, Daniel A.
AU - Gros-Louis, Francois
AU - Rouleau, Guy
AU - Horazdovsky, Bruce F.
AU - Leavitt, Blair R.
AU - Hayden, Michael R.
N1 - Funding Information:
We would like to acknowledge UBiC Resources and Support at the UBC Bioinformatics Centre, University of British Columbia, for assistance with bioinformatics. We would also like to thank Rona Graham and Kathy Banks for providing assistance and materials for mouse developmental stage immunoblots. This work was supported by the Canadian Institutes for Health Research grant #20R90753 and by grants from the ALS Association (M.R.H. and G.R.), the Huntington Society of Canada (M.R.H. and B.R.L.), the Hereditary Disease Foundation (M.R.H. and B.R.L.), the Canadian Genetic Diseases Network (M.R.H. and B.R.L.), and the HD Society of America (M.R.H.). R.S.D. was the recipient of a Wellcome Trust postdoctoral fellowship #060161. M.R.H. is a holder of a Canada Research Chair in Human Genetics. J.D.T. was supported by a National Science Foundation pre-doctoral fellowship. B.F.H. was supported by the National Institutes of Health (GM067206) and the Mayo Foundation.
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
KW - ALS2
KW - ALS2CL
KW - Alsin
KW - Cerebellum
KW - Endosome
KW - lacZ
UR - http://www.scopus.com/inward/record.url?scp=20144379753&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144379753&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2004.10.002
DO - 10.1016/j.nbd.2004.10.002
M3 - Article
C2 - 15686953
AN - SCOPUS:20144379753
SN - 0969-9961
VL - 18
SP - 243
EP - 257
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 2
ER -