Abstract
BackgroundADAM11 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.ResultsADAM11-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.ConclusionOur 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.
Highlights
ADAM11 is a member of the ADAM gene family and is mainly expressed in the nervous system
Generation of ADAM11-deficient mice Mice carrying a targeted mutation in their Adam11 gene were generated by homologous recombination (Fig. 1A)
As a result of this procedure, since a termination codon was introduced in exon 5 in the pro-protein domain, only the truncated form of the ADAM11 protein would be synthesised from this targeted allele
Summary
ADAM11 is a member of the ADAM gene family and is mainly expressed in the nervous system. To elucidate the physiological functions of ADAM11, we generated ADAM11-deficient mice by means of gene targeting. Half of the ADAMs are catalytically active metalloproteases that shed a broad range of substrates, such as cytokines, growth factors, receptors, adhesion molecules [1,2]. Recent gene-disruption studies in mice have disclosed a physiological role of each ADAM. The remaining half, which are non-protease-ADAMs, are thought to be adhesion molecules. More than ten ADAMs have been shown to support integrin-mediated cell adhesion in vitro [11]. The finding has been reported that integrin-mediated cell migration of tissue culture cells can be controlled by distinct ADAMs [12]. In C. elegans, unc-71 gene coding a non-protease-ADAM (page number not for citation purposes)
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