Rescue of cyclin D1 deficiency by knockin cyclin E

D-type cyclins and cyclin E represent two very distinct classes of mammalia n G1 cyclins. We have generated a mouse strain in which the coding sequence s of the cyclin D1 gene (Ccnd1) have been deleted and replaced by those of human cyclin E (CCNE). In the tissues and cells of these mice, the expressi on pattern of human cyclin E faithfully reproduces that normally associated with mouse cyclin D1. The replacement of cyclin D1 with cyclin E rescues a ll phenotypic manifestations of cyclin D1 deficiency and restores normal de velopment in cyclin D1-dependent tissues. Thus, cyclin E can functionally r eplace cyclin D1. Our analyses suggest that cyclin E is the major downstrea m target of cyclin D1.