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. Author manuscript; available in PMC: 2014 Aug 25.
Published in final edited form as: Cold Spring Harb Protoc. 2014 Apr 1;2014(4):339–349. doi: 10.1101/pdb.top069807

FIGURE 2.

FIGURE 2

Breeding schemes for generating Cre-lox conditional, tissue-specific mutant mice. (A) Classical Cre-lox strategy to obtain conditional gene knockout in a tissue-specific manner. Mice harboring the conditional allele are crossed with Cre transgenic mice, in which Cre recombinase is under the control of a tissue-specific promoter (TSP). Breeding of these two mice will produce heterozygous offspring with excision of the floxed gene of interest only in the Cre-expressing cells/tissue (gray), while the gene of interest remains functional in other cell/tissue types (white). Offspring that are heterozygous for the conditional allele and also contain the Cre transgene (G1) are crossed to homozygous conditional mutant mice. Offspring that are homozygous for the conditional allele and heterozygous for the Cre transgene (G2) represent the conditional deletion mice, which can be generated at a frequency of 25%. Littermates that are homozygous for the conditional allele but do not carry the Cre transgene can be used as experimental controls. (B) Ligand-inducible strategy to obtain conditional gene knockout. Mice harboring the conditional allele are crossed with mice carrying a CreER fusion protein that is under the control of a tissue specific promoter (TSP). Breeding of these two mice will produce heterozygous offspring that contain the floxed gene of interest and the CreER fusion transgene. These animals are crossed to homozygous conditional mutant mice (G1). Offspring that are homozygous for the conditional allele and heterozygous for the CreER transgene (G2) can be generated at a frequency of 25% and represent the experimental animals. In the presence of ligand (tamaxofin [4-OH]) the floxed gene of interest will be excised only in the CreER-expressing cells/tissue (gray), while the gene of interest remains functional in other cell/tissue types (white). Control animals are treated with vehicle and the floxed gene of interest remains functional in all cell/tissue types since the CreER transgene is not activated by the ligand.