In order to selectively inactivate genes in a tissue specific manner many laboratories have developed Cre transgenic mouse strains in which the Cre recombinase is expressed under the control of a tissue specific promoter. The Lck-Cre transgenic mouse uses the proximal promoter of the Lck (lymphocyte protein tyrosine kinase) gene, which is first expressed early in thymocyte development at the double negative stage.
After T cells fully mature, the level of expression of this transgene decreases by approximately 10 fold.
This particular mouse shows a high degree of expression of the transgene in the thymus and has been found to bring about the selective deletion of genes flanked by loxP targeting sequences in almost all early thymocytes.
It thus will be useful for experiments designed to delete a specific gene in the T cell lineage starting at the double negative stage.
Since the Lck-Cre transgene in this strain has been made homozygous, one can simply cross the mouse to any strain containing a floxed gene of interest and obtain offspring that have deleted it in this tissue specific manner.
If your strain is heterozygous, you can also obtain control animals in the same litter by typing for the presence or absence of the floxed gene in genomic DNA tail samples.
Dr. Chris Wilson has recently discovered that his Lck-Cre transgenic mouse can cause partial to complete deletion in non-lymphoid tissues in some mice on certain backgrounds.
These occurrences are unpredictable, but are apparent in tail DNA samples.
Investigators should determine whether this abnormality is present in their crosses.
Aberrant deletion had not been observed with the Cd4-Cre mouse (line 4196) developed by Dr. Wilson.
This model has replaced Model 4204-M. It has been further backcrossed to C57BL/6 for a total of 9 generations.
Genetic Background: C57BL/6 Background
The Lck-Cre transgenic mice were developed in the laboratories of Dr. Roger Perlmutter and Dr. Chris Wilson at the University of Washington. The Lck-Cre construct was created 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 Lck-Cre mice were created by pronuclear microinjection of this construct into B6DF2 fertilized eggs. These mice were first backcrossed three times to B6 and then bred to produce homozygotes. Later they were bred to mice of a mixed B6;129Sv/J background. The resultant STOCK-Tg(Lck-Cre)1Cwi mice were screened for H-2 expression and offspring homozygous for H-2b were selected for breeding. Homozygous Lck-Cre mice maintained on this mixed background were then transferred to the NIAID repository at Taconic for embryo rederivation by crossing with C57BL/6NTac mice. These pups were then backcrossed to C57BL/6NTac for a total of 9 generations. Those carrying the transgene were further intracrossed to homozygosity and selected for distribution. The NIAID Exchange Program has closed, and NIAID is no longer associated with provision of this strain. This strain is now stored as cryopreserved materials held by Taconic.
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