Reduced motor and sensory functions and emotional response in GM3-only mice: emergence from early stage of life and exacerbation with aging.
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.
Tajima
Orie
O
Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
Egashira
Nobuaki
N
Ohmi
Yuhsuke
Y
Fukue
Yoshihiko
Y
Mishima
Kenichi
K
Iwasaki
Katsunori
K
Fujiwara
Michihiro
M
Inokuchi
Jinichi
J
Sugiura
Yasuo
Y
Furukawa
Keiko
K
Furukawa
Koichi
K
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
D005679:G(M3) Ganglioside; D005732:Gangliosides; D017350:N-Acetylgalactosaminyltransferases; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase