The alpha(2) integrin subunit-deficient mouse: a multifaceted phenotype including defects of branching morphogenesis and hemostasis.
The alpha(2)beta(1) integrin is a collagen/laminin receptor expressed on platelets, endothelial cells, fibroblasts, and epithelial cells. To define the role of the alpha(2)beta(1) integrin in vivo, we created a genetically engineered mouse in which expression of the alpha(2)beta(1) integrin was completely eliminated. Mice deficient in the alpha(2)beta(1) integrin are viable, fertile, and develop normally with no excess lethality of homozygotes. Both alpha(2)beta(1)-integrin protein and alpha(2) mRNA were undetectable in the alpha(2)-null mice. Gross and histological evaluation of the heart, lungs, kidneys, gastrointestinal tract, pancreas, skin, and reproductive tracts revealed no abnormalities. However, quantitative analysis of mammary gland branching morphogenesis demonstrated that branching complexity is markedly diminished in the alpha(2)-deficient animals. Studies in the alpha(2)-deficient animals do not support the proposed roles for the alpha(2)beta(1) integrin on fibroblasts and keratinocytes in wound healing. When compared to platelets from wild-type littermates, platelets from alpha(2)-null mice failed to adhere to type I collagen under either static or shear-stress conditions. Although platelets from alpha(2)-deficient animals aggregated in response to collagen, they did so with prolonged lag time and lessened intensity. The alpha(2)beta(1) integrin-null mouse thus exhibits diverse, sometimes subtle, phenotypes consistent with the widespread pattern of alpha(2)beta(1) integrin expression.
Chen
Jianchun
J
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Diacovo
Thomas G
TG
Grenache
David G
DG
Santoro
Samuel A
SA
Zutter
Mary M
MM
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D005260:Female; D006487:Hemostasis; D039421:Integrin alpha2; D008297:Male; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010641:Phenotype; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D013997:Time Factors
D015703:Antigens, CD; D039421:Integrin alpha2