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Multidrug resistance gene expression during the murine ontogeny
M Schiengold1, L Schwantes, G Schwartsmann
1Genetics Department, Universidade Federal do Rio Grande do Sul Avenue Bento Gonçalves 9500-C.P. 15053, 91.501-970 Porto Alegre, Brazil. marion@if.ufrgs.br
Abstract:
Multidrug resistance (MDR) was described initially for tumor cells which become resistant not only to the specific drug to which they are submitted, but also to a large range of unrelated drugs. The expression of mdr genes, responsible for the phenotype, and their product P glycoprotein (Pgp), is currently under intensive study due to their ample distribution in different organisms and their possible physiological roles which include protection against xenobiotics. In mice, three mdr isoforms expressed in some normal tissues are known. In this work, we analyzed by RT-PCR the expression of mdr1, mdr2 and mdr3 in several organs of BALB/c and C57BL/6 mice during ontogeny. A considerable variation in mdr expression among individuals of the same strain, as well as among different organs in individuals of the same age group and among different age groups, was detected. We also observed a strong tendency for the expression of a greater number of active isoforms in old mice. The large expression range of the mdr isoforms point to an important role as a natural defense system.
Insights
Multidrug resistance (MDR) gene expression varies significantly across mouse organs and ages. Increased expression in older mice suggests a role for these genes in natural defense mechanisms.
Area of Science:
- Molecular Biology
- Genetics
- Immunology
Background:
- Multidrug resistance (MDR) involves resistance to various drugs, initially observed in tumor cells.
- MDR genes and their P glycoprotein (Pgp) product are studied for physiological roles, including xenobiotic protection.
- Three mdr isoforms are known in mice, expressed in normal tissues.
Purpose of the Study:
- To analyze the expression of mdr1, mdr2, and mdr3 isoforms in different mouse organs during development.
- To investigate variations in mdr gene expression across individuals, organs, and age groups in mice.
Main Methods:
- Reverse Transcription Polymerase Chain Reaction (RT-PCR) was used to quantify mdr isoform expression.
- Expression levels were analyzed in various organs of BALB/c and C57BL/6 mice across different developmental stages.
Main Results:
- Significant variations in mdr gene expression were observed among individual mice of the same strain.
- Expression levels differed across various organs within the same age group and across different age groups.
- A trend towards increased expression of multiple active mdr isoforms was noted in older mice.
Conclusions:
- MDR isoforms exhibit a broad expression range in mice, indicating a potential role in natural defense.
- Ontogenetic and inter-individual variability in mdr expression highlights complex regulatory mechanisms.
- The findings suggest that mdr genes contribute to the body's defense against foreign substances.