Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1

Lijin Dong, Yong Chen, Marcia Lewis, Jyh Cheng Hsieh, Janet Reing, J. Richard Chaillet, Carina Y. Howell, Mona Melhem, Sadayuki Inoue, Jerry R. Kuszak, Koen DeGeest, Albert E. Chung

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Entactin-1 (nidogen-1) is an ubiquitous component of basement membranes. From in vitro experiments, entactin-1 was assigned a role in maintaining the structural integrity of the basement membrane because of its binding affinity to other components, such as type IV collagen and laminin. Entactin-1 also interacts with integrin receptors on the cell surface to mediate cell adhesion, spreading, and motility. Targeted disruption of the entactin-1 gene in the mouse presented in this study revealed a duplication of the entacin-1 locus. Homozygous mutants for the functional locus lacked entactin-1 mRNA and protein and often displayed seizure-like symptoms and loss of muscle control in the hind legs. The behavior patterns suggested the presence of neurologic deficits in the central nervous system, thus providing genetic evidence linking entactin-1 to proper functions of the neuromuscular system. In homozygous mutants, structural alterations in the basement membranes were found only in selected locations including brain capillaries and the lens capsule. The morphology of the basement membranes in other tissues examined superficially appeared to be normal. These observations suggest that the lost functions of entactin-1 result in pathologic changes that are highly tissue specific.

Original languageEnglish (US)
Pages (from-to)1617-1630
Number of pages14
JournalLaboratory Investigation
Volume82
Issue number12
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Dong, L., Chen, Y., Lewis, M., Hsieh, J. C., Reing, J., Chaillet, J. R., Howell, C. Y., Melhem, M., Inoue, S., Kuszak, J. R., DeGeest, K., & Chung, A. E. (2002). Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1. Laboratory Investigation, 82(12), 1617-1630. https://doi.org/10.1097/01.LAB.0000042240.52093.0F