Chromosome instability and tumor predisposition inversely correlate with BLM protein levels
| Autor: | Mark J. Watson, Roger A. Schultz, Alexander D. Borowsky, Lisa D. McDaniel, Philip Leder, Nicholas Chester |
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| Rok vydání: | 2003 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Mutant Biology Biochemistry Embryonic and Fetal Development Mice Suppression Genetic Chromosomal Instability Neoplasms Chromosome instability Genotype medicine Animals Genetic Predisposition to Disease Bloom syndrome RNA Messenger Allele Molecular Biology Gene Adenosine Triphosphatases Mice Knockout RecQ Helicases urogenital system DNA Helicases nutritional and metabolic diseases Chromosome Cell Biology medicine.disease Molecular biology Phenotype Gene Targeting Embryo Loss Female Bloom Syndrome Spleen |
| Zdroj: | DNA Repair. 2:1387-1404 |
| ISSN: | 1568-7864 |
| Popis: | Independent mouse models for Bloom syndrome (BS) exist, each thought to disrupt Blm gene function. However, animals bearing these alleles exhibit distinct phenotypes. Blm tm1Ches and Blm tm1Grdn homozygous mutant animals exhibit embryonic lethality while in another, Blm tm3Brd , homozygosity yields viable, fertile animals with a cancer predisposition. Further characterization reveals the Blm tm3Brd allele to be a hypomorph, producing a diminished quantity of normal mRNA and protein. The Blm tm3Brd allele produces sufficient normal protein to rescue Blm tm1Ches lethality. Evaluation of viable animals reveals an inverse correlation between the quantity of Blm protein and the level of chromosome instability and a similar genotypic relationship for tumor predisposition indicating that Blm protein is rate limiting for maintaining genomic stability and the avoidance of tumors. |
| Databáze: | OpenAIRE |
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