title: Brain development in mice lacking L1-L1 homophilic adhesion.
abstract: 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-alpha5beta1 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-alpha5beta1 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.
authors.affiliation: Department of Neuroscience, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Itoh
authors.forename: Ling
authors.initials: L
authors.lastname: Cheng
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kamei
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiguchi
authors.forename: Paul
authors.initials: P
authors.lastname: Gutwein
authors.forename: Alexander
authors.initials: A
authors.lastname: Stoeck
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.forename: Vance
authors.initials: V
authors.lastname: Lemmon
mesh_terms: D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D058969:Contactin 2; D058966:Contactins; D005260:Female; D005804:Genes, Lethal / Q000235:genetics; D006849:Hydrocephalus / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007178:Inbreeding; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D039842:Neural Cell Adhesion Molecule L1 / Q000172:deficiency* / Q000235:genetics; D009434:Neural Pathways / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D058580:Neurocan; D039921:Neuropilins / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics
chemical_list: C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D011508:Chondroitin Sulfate Proteoglycans; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D058966:Contactins; D039081:Integrin alpha5beta1; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D058580:Neurocan; D039921:Neuropilins; C076817:NCAN protein, human