Cyclin D2 overexpression in transgenic mice induces thymic and epidermal hyperplasia whereas cyclin D3 expression results only in epidermal hyperplasia

In a previous report, we described the effects of cyclin D1 expression in e pithelial tissues of transgenic mice. To study the involvement of D-type cy clins (D1, D2, and D3) in epithelial growth and differentiation and their p utative role as oncogenes in skin, transgenic mice were developed which car ry cyclin D2 or D3 genes driven by a keratin 5 promoter. As expected, both transgenic lines showed expression of these proteins in most of the squamou s tissues analyzed. Epidermal proliferation increased in transgenic animals and basal cell hyperplasia was observed. All of the animals also had a min or thickening of the epidermis, The pattern of expression of keratin 1 and keratin 5 indicated that epidermal differentiation was not affected, Transg enic K5D2 mice developed mild thymic hyperplasia that reversed at 4 months of age, On the other hand, high expression of cyclin D3) in the thymus did not produce hyperplasia, This model provides in vivo evidence of the action of cyclin D2 and cyclin D3 as mediators of proliferation in squamous epith elial cells. A direct comparison among the three D-type cyclin transgenic m ice suggests that cyclin D1 and cyclin D2 have similar roles in epithelial thymus cells. However, overexpression of each D-type cyclin produces a dist inct phenotype in thymic epithelial cells.