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3.2 kb of the gene including part of exon 15 and all of exon 16 was replaced with a IRES-lacZ-neo cassette via homologous recombination resulting in deletion of the C-terminal region encoding ubiquitin protein ligase activity. Absence of gene expression in animals carrying a mutant maternal allele was confirmed by Western blot analysis. Beta-gal staining of brain sections from maternal-deficient animals showed high levels of lacZ activity in the hippocampus, dentate gyrus, ventricular ependyma, and in scattered cells throughout the frontal cortex. (J:75622)