All experiments involving live animals were conducted with the approval of the City of Hope institutional animal care and use committee. Mice used in the derivation of transgenic mice were maintained on a 14 hr light/10 hr dark cycle. Female mice (FVB/ NJ, Jackson Laboratories) were superovulated with 5 IU of pregnant-mare serum-gonadotropin (National Hormone and Peptide Program, UCLA, Los Angeles, CA) followed 48 hours later by 5 IU of human-chorionic gonadotropin (Sigma-Aldrich, St. Louis MO) and mating to fertile FVB/NJ males. Fertilized oocytes were collected ,12 to 14 hours after the middle of the dark cycle, and treated briefly with bovine hyaluronidase in M2 medium to remove the cumulus cells. Immediately prior to microinjection the purified BAC DNA was diluted to a concentration of 3 ng/mL in 1 mM Tris-HCl (pH 8.0), 0.1 mM EDTA, 100 mM NaCl containing 30 mM spermine/70 mM spermidine [31] . The BAC DNA solution was microinjected into the pronuclei of fertilized oocytes using standard techniques, and the manipulated oocytes were transferred surgically into the oviducts of 0.5 dpc pseudo-pregnant recipient female mice and allowed to develop to full term.