Biomedical subjects
Publications and source records attributed to C P Landel.
The production of transgenic mice is a technology of great utility in the dissection of complex biological processes. This article is intended as a detailed primer for people interested in learning to produce transgenic mice, and discusses equipment, methods, and future directions for this technique.
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An expression system for cell lineage ablation in transgenic mice was constructed in which a modified form of the A subunit of ricin, a toxic lectin produced by the castor bean Ricinus communis, can be expressed under the direction of tissue-specific regulatory signals. A chimeric gene was formed by fusing the promoter and 5'-flanking sequences of the lens-specific mouse alpha A-crystallin gene with a modified ricin A cDNA, and this construction was integrated into the germ line of transgenic mice. These animals develop profound microphthalmia with severe developmental defects of the eye, relating primarily to the disorganization and death of cells forming the lens. In addition, this defect is associated with several abnormalities, including eye size, folding of the retina, and ectopic lens material in other regions of the eye. The phenotype of this engineered developmental mutation suggests that the normal development of alpha A-crystallin-producing lens fiber cells is essential for the proper growth, organization, and orientation of optic structures.
The Thy-1 antigen is a cell-surface glycoprotein of unknown function expressed on mouse T lymphocytes, neurons, and hematopoietic stem cells. To alter the normal pattern of Thy-1 expression during hematopoietic differentiation, we created transgenic mice using a hybrid Thy-1 gene containing a transcriptional enhancer of the mouse immunoglobulin heavy chain gene (E mu). Strains of mice bearing the Thy-1.2/E mu gene express the Thy-1.2 antigen on mature B lymphocytes and their progenitors, and develop a heritable lymphoid hyperplasia characterized by massive expression of the Thy-1.2 antigen in the bone marrow and lymph nodes. The phenotype associated with inappropriate developmental regulation of the Thy-1 gene suggests that the Thy-1 antigen may play a role in inducing activation or differentiation events on early lymphocyte progenitor cells.