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(American Journal of Pathology. 2002;161:337-344.)
© 2002 American Society for Investigative Pathology

Animal Models

The {alpha}2 Integrin Subunit-Deficient Mouse

A Multifaceted Phenotype Including Defects of Branching Morphogenesis and Hemostasis

Jianchun Chen*, Thomas G. Diacovo{dagger}, David G. Grenache*, Samuel A. Santoro* and Mary M. Zutter*

From the Departments of Pathology and Immunology*and Pediatrics,{dagger}Washington University School of Medicine, St. Louis, Missouri

Abstract

The {alpha}2ß1 integrin is a collagen/laminin receptor expressed on platelets, endothelial cells, fibroblasts, and epithelial cells. To define the role of the {alpha}2ß1 integrin in vivo, we created a genetically engineered mouse in which expression of the {alpha}2ß1 integrin was completely eliminated. Mice deficient in the {alpha}2ß1 integrin are viable, fertile, and develop normally with no excess lethality of homozygotes. Both {alpha}2ß1-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}2ß1 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}2ß1 integrin-null mouse thus exhibits diverse, sometimes subtle, phenotypes consistent with the widespread pattern of {alpha}2ß1 integrin expression.




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