ENU mouse mutagenesis: Generation of mouse mutants with aberrant plasma IgE levels

Background: The ENU Mouse Mutagenesis Project aims at a large-scale, system atic production of mouse mutants using the alkylating agent ethyl-nitrosour ea (ENU). Offspring of mutagenized mice are subjected to a multiparameter s creen to detect alterations in various phenotypes with the ultimate goal of identifying novel genes relevant for the expression of the phenotype. Usin g this approach, we have analyzed plasma IgE concentrations to identify mou se mutants with aberrant plasma IgE levels. Methods and Results: ENU-mutage nized male C3HeB/FeJ were mated to wild-type females to produce F1 offsprin g. F1 animals were analyzed for alterations in their plasma IgE concentrati ons that showed a dominant mode of inheritance, or bred further to screen f or recessive phenotypes. Plasma IgE concentrations were deter mined by ELIS A and a normal range for plasma IgE was established using C3HeB/FeJ wild-ty pe animals. So far we have tested 6568 F1 animals. Repeated testing confirm ed a stable aberrant IgE phenotype in 124 animals. To confirm the genetic b asis of the observed phenotype, these mice were subjected to confirmation c rossing. Currently we have established 9 independent m uta nt mouse lines ( 3 with high plasma IgE and 6 with plasma IgE below detection limit) that ha ve been genetically confirmed and additional 24 variant mouse lines are cur rently undergoing confirmation testing. Conclusion: ENU mouse mutagenesis a llowed us to generate and identify mouse mutants with aberrant plasma IgE l evels, which may be used to characterize novel genes involved in IgE regula tion and may serve as animal models for IgE-mediated diseases. Copyright (C ) 2001 S. Karger AG, Basel.