International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Plenary Presentations * Oral Presentations *
Poster Presentations: Complex Genetics and Disease Modifiers * Developmental Genetics * Functional Genomics * Gene Discovery * Genetic Manipulations to Alter Gene Function * Mouse Models: Human Disease and Pharmacogenetics * Sequence Annotation and Comparative Analysis of Genomes *
Attendees * Sponsors * Table of Contents * Photographs * Awards

Oral Presentation

Wednesday 20 November

16:30 - 16:45 HRS

Cx32 KNOCKOUT MOUSE AND LEUKEMOGENESIS

Y Hirabayashi
Div. Cellular and Molecular Toxicology, National Institute of Health Sciences

Co-Authors: 1) Yoon BI, 1) Tsuboi I, 1) Huo Y, 1) Kodama Y, 2) Otto T, 1) Kanno J, 2) Willecke K,  3) Trosko JE, and Inoue T.
Institutions: 1) National Institute of Health Sciences, 2) Institut für Genetik, Bonn Universitaet, 3) Department of Pediatrics and Human Development, Michigan State University, College of Human Medicine

Several gap-junction (GJ) genes, connexins, have been shown to be involved with fundamental cellular functions, such as regulation of cell growth, cell differentiation, programmed cell death or apoptosis, and synchronization of electronic and metabolic functions of cells. Use of mice with various GJ genes, genetically “knocked out”, has also linked these genes to a number of diseases, including tumorigenesis and also embryonal lethality, heart defects, and sensory nerve disturbances including cochlear neuropathy. Furthermore, humans who inherit specific mutated gap junction genes are associated with a number of diseases; e.g. Connexin32 (Cx32) for the X-linked Charcot-Marie-Tooth Disease (CMTX). Indirect evidence, such as growth factors and chemicals that inhibit GJ function can inhibit cell death or apoptosis and stimulate cell growth on one hand and to encourage tumorigenesis on the other hand. Thus, in this study, a controversial question as to whether the role played by GJs is protective against or promotive of tumorigenesis is tried to answered, because a lack of GJs, on one hand, inhibits apoptosis of cell damaged by carcinogens, and, on the other hand, it is supposed that those potentially initiated and promoted cells undergo independent cell growth which may lead to tumorigenesis. This study, first of its kind, demonstrates that Cx32 functions in the bone marrow, and, when knocked out, thereby plays a role in leukemogenesis by encouraging a general neoplastic outcome after chemical carcinogen exposure. Thus, implications towards risks of potential induction of leukemia during a clinical course of the CMTX patient may not be accidental.