Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1.
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.
Dong
Lijin
L
Department of Obstetrics and Gynecology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. ldong@rush.edu
Chen
Yong
Y
Lewis
Marcia
M
Hsieh
Jyh-Cheng
JC
Reing
Janet
J
Chaillet
J Richard
JR
Howell
Carina Y
CY
Melhem
Mona
M
Inoue
Sadayuki
S
Kuszak
Jerry R
JR
DeGeest
Koen
K
Chung
Albert E
AE
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D001522:Behavior, Animal / Q000502:physiology; D015139:Blotting, Southern; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply; D002135:Calcium-Binding Proteins; D002196:Capillaries / Q000648:ultrastructure; D015815:Cell Adhesion Molecules; D020820:Dyskinesias / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D007124:Immunoenzyme Techniques; D007903:Lens Capsule, Crystalline / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology*
D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; C112846:Nid2 protein, mouse; D012333:RNA, Messenger; C029967:nidogen