The Cd4-Cre Transgenic mouse was originally developed in the laboratory of Dr. Chris Wilson at the University of Washington. The Cd4-Cre construct was created by replacing the the lck proximal promoter of a construct used to make a Lck-Cre Transgenic mouse (Taconic line 4197) with the mouse Cd4 promoter/enhancer/silencer, which was provided by Dr. Dan Littman and Dr. Nigel Killeen. The original Lck-Cre mouse, which was generated in the laboratories of Wilson and Perlmutter, was designed by engineering a nuclear localization signal and optimum eukaryotic translation start site at the 5' end of Cre and inserting this downstream of the Lck proximal promoter. The Cd4-Cre mouse was created by pronuclear injection of the Cd4-Cre construct into B6D2F2 fertilized eggs. The founder line was first crossed three times to the C57BL/6J strain, and then bred to produce homozygotes. Later they were crossed to mice of a mixed B6;129Sv/J background. The resultant STOCK-Tg(Cd4-Cre) mice were screened for H-2 expression and offspring homozygous for H-2b were selected for breeding. Homozygous mice maintained on this mixed background were then transferred to the NIAID repository at Taconic for embryo rederivation by crossing with C57BL/6NTac mice. The ET derived mice were crossed one additional generation to C57BL/6NAi mice. PCR analysis was used to confirm that the derived pups carried the Cd4-Cre transgene. These pups were then backcrossed to C57BL/6NTac from N4 to N9. The line was then intracrossed to homozygosity.
Lee PP, Fitzpatrick DR, Beard C, Jessup HK, Lehar S, Makar KW, Perez- Melgosa M, Sweetser MT, Schlissel MS, Nguyen S, Cherry SR, Tsai JH, Tucker SM, Weaver WM, Kelso A, Jaenisch J and Wilson CB. A critical role for Dnmt1 and DNA methylation in T cell development, function and survival. Immunity Nov. 2001,15(5) 763-74.