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Gene targeting for inflammatory cell adhesion molecules
D C Bullard1, E T Sandberg, K Scharffetter-Kochanek
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
Using gene targeting in mouse embryonic stem cells, it is possible to introduce diverse mutations into specific genes. Using these methods, various laboratories have reported mutations for a variety of inflammatory cell adhesion molecules including CD18, alpha 5 integrin, ICAM-1, P-selectin, and L-selectin; preliminary reports of other mutations are also available. Mutations in CD18 and ICAM-1 cause impaired inflammatory and immune responses, mutations in P-selectin and L-selectin cause decreased leukocyte rolling and emigration, and a mutation in alpha 5 integrin causes embryonic lethality. Gene targeting complements other approaches for analyzing the function of inflammatory cell adhesion molecules.
Insights
Gene targeting in mice creates mutations in inflammatory cell adhesion molecules. These genetic modifications reveal crucial roles for molecules like CD18 and ICAM-1 in immune responses and leukocyte behavior.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Inflammatory cell adhesion molecules (ICAMs) play critical roles in immune responses.
- Understanding the function of ICAMs is essential for developing new therapeutic strategies.
- Gene targeting offers a powerful method to study gene function in vivo.
Purpose of the Study:
- To investigate the functional roles of various inflammatory cell adhesion molecules.
- To demonstrate the utility of gene targeting in creating specific mutations in ICAMs.
- To analyze the impact of these mutations on cellular and organismal functions.
Main Methods:
- Gene targeting in mouse embryonic stem cells to introduce specific mutations.
- Generation of knockout mice for selected inflammatory cell adhesion molecules.
- Phenotypic analysis of mutant mice to assess immune and inflammatory responses.
Main Results:
- Mutations in CD18 and ICAM-1 resulted in impaired inflammatory and immune responses.
- P-selectin and L-selectin mutations led to decreased leukocyte rolling and emigration.
- Alpha 5 integrin mutation caused embryonic lethality, highlighting its essential role.
Conclusions:
- Gene targeting is a valuable tool for dissecting the functions of inflammatory cell adhesion molecules.
- Specific ICAMs are crucial for leukocyte trafficking and immune cell function.
- Understanding ICAM function through genetic manipulation aids in comprehending inflammatory processes.