Deficits in spatial learning and motor coordination in ADAM11-deficient mice.
BACKGROUND
ADAM11 is a member of the ADAM gene family and is mainly expressed in the nervous system. It is thought to be an adhesion molecule, since it has a disintegrin-like domain related to cell-cell or cell-matrix interactions. To elucidate the physiological functions of ADAM11, we generated ADAM11-deficient mice by means of gene targeting.


RESULTS
ADAM11-deficient mice were apparently normal, and survived more than one year with no major histological abnormalities in the brain or spinal cord. Because ADAM11 is highly expressed in the hippocampus and cerebellum, we have examined ADAM11 mutant mice for learning using visual and hidden water maze tasks, and their motor coordination using a rotating rod task. Our results showed that their visual water maze task results are normal, but the hidden water maze and rotating rod task skills are impaired in ADAM11-deficient mice.


CONCLUSIONS
Our results indicate that ADAM11 mutation does not affect cell migration and differentiation during development, but affects learning and motor coordination. Thus, ADAM11 might play an important signalling or structural role as a cell adhesion molecule at the synapse, and may thus participate in synaptic regulation underlying behavioural changes.
Takahashi
Eiki
E
Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. e2-takahashi@hhc.eisai.co.jp
Sagane
Koji
K
Oki
Tohru
T
Yamazaki
Kazuto
K
Nagasu
Takeshi
T
Kuromitsu
Junro
J
D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D018390:Gene Targeting; D007858:Learning; D018782:Maze Learning; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills; D013037:Spatial Behavior
D008565:Membrane Proteins; C107204:ADAM 11 protein, mouse; D051722:ADAM Proteins