Gene targeting of BPAG1: abnormalities in mechanical strength and cell migration in stratified epithelia and neurologic degeneration.
BPAG1 is the major antigenic determinant of autoimmune sera of bullous pemphigoid (BP) patients. It is made by stratified squamous epithelia, where it localizes to the inner surface of specialized integrin-mediated adherens junctions (hemidesmosomes). To explore the function of BPAG1 and its relation to BP, we targeted the removal of the BPAG1 gene in mice. Hemidesmosomes are otherwise normal, but they lack the inner plate and have no cytoskeleton attached. Though not affecting cell growth or substratum adhesion, this compromises mechanical integrity and influences migration. Unexpectedly, the mice also develop severe dystonia and sensory nerve degeneration typical of dystonia musculorum (dt/dt) mice. We show that in at least one other strain of dt/dt mice, BPAG1 gene is defective.
Guo
L
L
Howard Hughes Medical Institute, University of Chicago, Illinois 60637, USA.
Degenstein
L
L
Dowling
J
J
Yu
Q C
QC
Wollmann
R
R
Perman
B
B
Fuchs
E
E
D000818:Animals; D001324:Autoantigens / Q000235:genetics* / Q000302:isolation & purification; D002352:Carrier Proteins; D002465:Cell Movement; D003094:Collagen; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000473:pathology / Q000648:ultrastructure; D003896:Desmosomes / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D004421:Dystonia / Q000235:genetics; D000071821:Dystonin; D004848:Epithelium / Q000002:abnormalities; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics*; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D011984:Sensory Receptor Cells / Q000473:pathology*; D012868:Skin Abnormalities; D013718:Tensile Strength; D014945:Wound Healing / Q000235:genetics; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D012333:RNA, Messenger; D000097805:Collagen Type XVII; C095667:Dst protein, mouse