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Published online 5 April 2004. doi:10.1083/jcb.200312107
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 165, Number 1, 145-154
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Article

Brain development in mice lacking L1–L1 homophilic adhesion

Kyoko Itoh1,2, Ling Cheng1, Yoshimasa Kamei1, Shinji Fushiki2, Hiroyuki Kamiguchi3, Paul Gutwein4, Alexander Stoeck4, Bernd Arnold5, Peter Altevogt4, and Vance Lemmon1,6

1 Department of Neuroscience, Case Western Reserve University, Cleveland, OH 44106
2 Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan
3 Developmental Brain Science Group, RIKEN Brain Science Institute, Saitama 351-0198, Japan
4 D010, German Cancer Research Center, D-69120 Heidelberg, Germany
5 D050 Tumor Immunology Program, German Cancer Research Center, D-69120 Heidelberg, Germany
6 The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL 33136

Address correspondence to Vance Lemmon, The Miami Project to Cure Paralysis, University of Miami School of Medicine, Lois Pope LIFE Center, Room 4-16, 1095 NW 14th Terrace, Miami, FL 33136. Tel.: (305) 243-6793. Fax: (305) 243-3160. email: vlemmon{at}miami.edu

A new mouse line has been produced in which the sixth Ig domain of the L1 cell adhesion molecule has been deleted. Despite the rather large deletion, L1 expression is preserved at normal levels. In vitro experiments showed that L1–L1 homophilic binding was lost, along with L1-{alpha}5ß1 integrin binding. However, L1–neurocan and L1–neuropilin binding were preserved and sema3a responses were intact. Surprisingly, many of the axon guidance defects present in the L1 knockout mice, such as abnormal corticospinal tract and corpus callosum, were not observed. Nonetheless, when backcrossed on the C57BL/6 strain, a severe hydrocephalus was observed and after several generations, became an embryonic lethal. These results imply that L1 binding to L1, TAG-1, or F3, and L1-{alpha}5ß1 integrin binding are not essential for normal development of a variety of axon pathways, and suggest that L1–L1 homophilic binding is important in the production of X-linked hydrocephalus.

Key Words: adhesion; hydrocephalus; L1cam; corticospinal tract; integrin


Abbreviations used in this paper: CNS, central nervous system; DRG, dorsal root ganglion; FN, fibronectin; KO, knockout; wt, wild-type.


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