Rescue of cyclin D1 deficiency by knockin cyclin E.
D-type cyclins and cyclin E represent two very distinct classes of mammalian G1 cyclins. We have generated a mouse strain in which the coding sequences 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 expression pattern of human cyclin E faithfully reproduces that normally associated with mouse cyclin D1. The replacement of cyclin D1 with cyclin E rescues all phenotypic manifestations of cyclin D1 deficiency and restores normal development in cyclin D1-dependent tissues. Thus, cyclin E can functionally replace cyclin D1. Our analyses suggest that cyclin E is the major downstream target of cyclin D1.
Geng
Y
Y
Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Whoriskey
W
W
Park
M Y
MY
Bronson
R T
RT
Medema
R H
RH
Li
T
T
Weinberg
R A
RA
Sicinski
P
P
D000818:Animals; D019938:Cyclin D1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011960:Receptors, Estrogen / Q000378:metabolism; D012160:Retina / Q000378:metabolism
D019927:Cyclin E; D011960:Receptors, Estrogen; D019938:Cyclin D1