Table 2.

Developmental abnormalities associated with CDK4 and CDK6 deficiency

Disrupted gene(s)	Survival	Pathology	References
CDK4	viable	Small body size. Most males are sterile due to hypoplastic testes and low sperm counts. Female sterility is due to defects in the hypothalmic–pituitary axis, abnormal estrus, and failure of corpus luteum. Abnormal development of pancreatic β-islet cells leads to insulin-dependent diabetes within the first 2 months of life. MEFs can be propagated in culture with decreased ability to enter the cell cycle from quiescence; they express aberrantly high levels of p21Cip1 and resist transformation by oncogenic Ras + DN-p53.	(Moons et al., 2002a; Moons et al., 2002b; Rane et al., 1999; Tsutsui et al., 1999; Zou et al., 2002)
CDK6	viable	Thymic and splenic hypoplasia, and mild defects in hematopoiesis. T-lymphocytes exhibit delayed S-phase entry.	(Malumbres et al., 2004)
CDK4 and CDK6	progressive embryonic lethality from E14.5 onward; a few pups die after birth.	Small embryos. Partial failure of hematopoiesis results from reduced multi-potential progenitors and multi-lineage deficits, including severe megaloblastic anemia. MEFs proliferate with increased generation time and reduced Sphase fraction. Some D-type Cyclins associate with and activate CDK2. MEFs resist transformation.	(Malumbres et al., 2004)