This document describes a technique for generating a chimera mouse with a targeted gene disruption using Cre-lox recombination. ES cells containing flanking loxP sites around a gene of interest and a selectable marker are microinjected into blastocysts. The blastocysts are then implanted into a foster mother, generating a chimera mouse that can inherit the targeted gene disruption through germline transmission.

1. loxP loxP
neo
loxP loxP
neo
F1 ChimeraFoster Mother
WT
WT with specific promoter
loxP loxP
FRT
FRT FRT
FRT
FRT
exon
Cre mouse
(heterozygous)
3 - 5 Day old
blastocyst
Microinjection of ES
cells with targeted
gene disruption
Implant of blastocyst into a
pseudo-pregnant foster mother
Mouse with inherited
tissue colors
Cß2
exon
Cß2
exon
Cß2