International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

I7 Moe1, An ENU Induced Mutation Isolated from a Modifier Screen for Enhancers of E2A in Lymphocyte Development

Yuan Zhuang, Andrew Peterson, Nabil Habash, and Mei Fang Dai. Department of Immunology and Department of Genetics, Duke University Medical Center, Durham, NC 27710, USA

Lymphocyte development represents a unique and simple developmental model for genetic analysis of gene function in mice. B- and T-lymphocytes are the cellular components of the adaptive immune system, which is dispensable for mice kept in a clean facility. Because lymphocytes are constantly renewed from the hematopoietic stem cells throughout life, phenotypic analysis may be performed either in fetal stage or in adult mice. Multi-color flow cytometry analysis of lineage and stage specific markers also greatly facilitates the identification and characterization of lymphoid specific mutations.

Genetic and biochemical studies have demonstrated that the bHLH transcription factors encoded by the E2A gene play critical roles in the initiation, differentiation, and function of B-lymphocytes. However, how E2A controls B-cell specific gene expression and the differentiation program are not fully understood. To further investigate the regulatory pathways mediated by E2A gene products in lymphopoiesis, we have conducted a modifier screen to search for novel mutations which genetically interact with E2A. Evidence from earlier work has shown that the pro-B cell number in E2A heterozygous animals is reduced to one half of the wild type level. This phenotype is further enhanced in mice compound heterozygous for E2A and other B-cell regulatory genes such as EBF, E2-2, and HEB. We hypothesized that a genetic screen may recover E2A modifiers simply based on their abilities to reduce pro-B cell numbers on the E2A heterozygous background. Moe1 was isolated and characterized in the initial screen of 45 ENU derived F1 progeny. Moe1 is required for pre-B and pre-T cell development. No mature lymphocytes are found in Moe1 mutant homozygous mice. Adoptive transfer test has demonstrated that this function of Moe1 is restricted to lymphoid lineages. The general strategy of the modifier screen and the latest results of phenotypic analysis and meiotic mapping on Moe1 will be presented.


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