title: Reduced motor and sensory functions and emotional response in GM3-only mice: emergence from early stage of life and exacerbation with aging.
abstract: Sialic acid-containing glycosphingolipids (gangliosides) have been believed to play a role in the regulation and protection of nervous tissues. To clarify their function in the nervous system in vivo, double knockout (DKO) mice of GM2/GD2 synthase and GD3 synthase genes were generated and abnormal behaviors were analyzed. Mutant mice exhibited reduced weight and a round shape of the whole brain that progressively emerged with aging, and displayed motor dysfunction in the footprint, traction, open-field, and 24h locomotion activity tests. Sensory functions were also reduced in the von Frey and hot plate tests and greatly reduced in the acoustic startle response test. For emotional behavior, fear response was clearly decreased. Numerous neuronal dysfunctions were found even in younger mutant mice examined at 10-23 weeks after birth, which were exacerbated with aging. These results suggest that a lack of gangliosides other than GM3 induces severe neuronal degeneration in the early stage of life, and that the expression of complex gangliosides is essential to maintain the integrity of the nervous system throughout life.
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Orie
authors.initials: O
authors.lastname: Tajima
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Yuhsuke
authors.initials: Y
authors.lastname: Ohmi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fukue
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Jinichi
authors.initials: J
authors.lastname: Inokuchi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugiura
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000473:pathology; D005239:Fear / Q000502:physiology*; D005679:G(M3) Ganglioside / Q000502:physiology*; D005732:Gangliosides / Q000235:genetics / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009154:Mutation / Q000235:genetics; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D013216:Reflex, Startle / Q000502:physiology; D012677:Sensation / Q000502:physiology; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics*; D015431:Weight Loss / Q000502:physiology
chemical_list: D005679:G(M3) Ganglioside; D005732:Gangliosides; D017350:N-Acetylgalactosaminyltransferases; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase