Sensitivity to low-level radiation in radiosensitive 'wasted' mice
| Autor: | Gayle E. Woloschak, Tatjana Paunesku, Miroslava Protic |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Mutation
Mutant Public Health Environmental and Occupational Health General Medicine Biology Motor neuron medicine.disease_cause medicine.disease Radiation Dosage Molecular biology Mice Mutant Strains Proliferating cell nuclear antigen Mice Radiation Injuries Experimental Radiation sensitivity medicine.anatomical_structure Apoptosis Proliferating Cell Nuclear Antigen Immunology medicine biology.protein Animals Gene Immunodeficiency |
| Zdroj: | Military medicine. 167 |
| ISSN: | 0026-4075 |
| Popis: | Mice homozygous for the autosomal recessive "wasted" mutation (wst/wst) have abnormalities in T lymphocytes and in the anterior motor neuron cells of the spinal cord, leading to sensitivity to low doses of ionizing radiation, hind limb paralysis, and immunodeficiency. This defect results in a failure to gain weight by 20 days of age and death by 28 days. The wasted mutation (previously mapped to mouse chromosome 2) is shown to be a 3-bp deletion in a T cell-specific (and perhaps motor-neuron-specific) regulatory region (promoter) of the proliferating cell nuclear antigen (PCNA) gene on mouse chromosome 2. A regulatory element is also shown to be important in PCNA expression in T lymphocytes and motor neuron cells affected by the 3-bp deletions in the PCNA promoter. The model is as follows. Absence of PCNA expression in the thymuses (and motor neurons) of wasted mice causes cellular apoptosis. This absence of expression is mediated by a positive transfactor that can bind to the wild-type but not to the wasted mutant PCNA promoter. The bound protein induces late expression of PCNA in T lymphocytes and prevents onset of radiation sensitivity in the cells. |
| Databáze: | OpenAIRE |
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