caa a22 4500 397574916 CHVBK 20180308164852.0 cr unu---uuuuu 161202e199601 xx s 000 0 eng 10.1093/hmg/5.1.1 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.1.1 Dramatically Different Phenotypes in Mouse Models of Human Tay-Sachs and Sandhoff Diseases [Elektronische Daten] [Daniel Phaneuf, Nobuaki Wakamatsu, Jing-Qi Huang, Anita Borowski, Alan C. Peterson, Sheila R. Fortunato, Gerd Ritter, Suleiman A. Igdoura, Carlos R. Morales, Guylaine Benoit, Beverly R. Akerman, Daniel Leclerc, Nobuo Hanai, Jamey D. Marth, Jacquetta M. Trasler, Roy A. Gravel] We have generated mouse models of human Tay-Sachs and Sandhoff diseases by targeted disruption of the Hexa (α subunit) or Hexb (β subunit) genes, respectively, encoding lysosomal β-hexosaminidase A (structure, α) and B (structure, ββ). Both mutant mice accumulate GM2 ganglioside in brain, much more so in Hexb −/− mice, and the latter also accumulate glycolipid GA2. Hexa −/− mice suffer no obvious behavioral or neurological deficit, while Hexb −/− mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia. The Hexb −/− but not the Hexa −/− mice have massive depletion of spinal cord axons as an apparent consequence of neuronal storage of GM2. We propose that Hexa −/− mice escape disease through partial catabolism of accumulated GM2 via GA2 (asialo-GM2) through the combined action of sialidase and β-hexosaminidase B. © 1996 Oxford University Press Phaneuf Daniel Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut Wakamatsu Nobuaki Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut Huang Jing-Qi Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut Borowski Anita Biomedical Research Centre, University of British Columbia, Vancouver, Canada aut Peterson Alan C. The Royal Victoria Hospital Research Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada aut Fortunato Sheila R. Ludwig Institute for Cancer Research, New York Unit at the Memorial Sloan-Kettering Cancer Center, New York, USA aut Ritter Gerd Ludwig Institute for Cancer Research, New York Unit at the Memorial Sloan-Kettering Cancer Center, New York, USA aut Igdoura Suleiman A. Department of Anatomy and Cell Biology, McGill University, Montreal, Canada aut Morales Carlos R. Department of Anatomy and Cell Biology, McGill University, Montreal, Canada aut Benoit Guylaine Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut Akerman Beverly R. Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut Leclerc Daniel Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut Hanai Nobuo Division of Immunology, Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, Tokyo, Japan aut Marth Jamey D. Biomedical Research Centre, University of British Columbia, Vancouver, Canada aut Trasler Jacquetta M. Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut Gravel Roy A. Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut Human Molecular Genetics Oxford University Press 5/1(1996-01), 1-14 0964-6906 5:1<1 1996 5 hmg https://doi.org/10.1093/hmg/5.1.1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.1.1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Phaneuf Daniel Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Wakamatsu Nobuaki Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Huang Jing-Qi Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Borowski Anita Biomedical Research Centre, University of British Columbia, Vancouver, Canada aut NATIONALLICENCE 700 1- Peterson Alan C. The Royal Victoria Hospital Research Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Fortunato Sheila R. Ludwig Institute for Cancer Research, New York Unit at the Memorial Sloan-Kettering Cancer Center, New York, USA aut NATIONALLICENCE 700 1- Ritter Gerd Ludwig Institute for Cancer Research, New York Unit at the Memorial Sloan-Kettering Cancer Center, New York, USA aut NATIONALLICENCE 700 1- Igdoura Suleiman A. Department of Anatomy and Cell Biology, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Morales Carlos R. Department of Anatomy and Cell Biology, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Benoit Guylaine Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Akerman Beverly R. Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Leclerc Daniel Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Hanai Nobuo Division of Immunology, Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, Tokyo, Japan aut NATIONALLICENCE 700 1- Marth Jamey D. Biomedical Research Centre, University of British Columbia, Vancouver, Canada aut NATIONALLICENCE 700 1- Trasler Jacquetta M. Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut NATIONALLICENCE 700 1- Gravel Roy A. Research Institute, Montreal Children's Hospital, Departments of Pediatrics and Human Genetics, McGill University, Montreal, Canada aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/1(1996-01), 1-14 0964-6906 5:1<1 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford