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.
We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.
We present evidence that associates dominant mutations in Caenorhabditis elegans that disrupt muscle structure and motility with a cluster of three actin genes mapped in the same region of linkage group V. We examined spontaneous and mutagen-induced wild-type revertants of these dominant alleles for alterations in the DNA of the actin gene cluster. Four of 73 revertants contain detectable DNA rearrangements within the cluster of actin genes including an insertion, a deletion and gene fusions. We postulate that these rearrangements inactivate or delete at least one gene in the cluster and consequently the original mutations are within the actin gene cluster.