436 RISK ANALYSIS OF α-LACTALBUMIN TRANSGENE TRANSFER TO NONTRANSGENIC CONTROL ANIMALS DURING REARING, BREEDING, PARTURITION AND LACTATION

Abstract

Assessment of general risk posed from transgenic (T) animals is important to their future contributions to society. Identification of potentially harmful properties of transgenic livestock is the initial step in a risk assessment. We previously developed and characterized transgenic swine containing a mammary-specific transgene (bovine a-lactalbumin, bALAC) that results in increased milk production in sows. We are currently determining whether bALAC is expressed in tissues of T swine other than the lactating mammary gland and whether the transgene DNA (Tg) crosses into nontransgenic control (C) swine under various physiological and physical conditions. The specific aims addressed in the present study were to determine (1) whether the Tg can be transferred directly by physical association or contact; (2) whether the Tg can be transferred directly via mating; (3) whether the Tg can be transferred directly during gestation and parturition; and (4) whether the Tg can be transferred directly during lactation. The T animals utilized in these studies are in at least generation 10 and have stable incorporation of the Tg. Comparable age- and weight-matched animals, T and C, were housed together allowing general contact that is normal in swine production, for either 180, 220, or 250 days of age after weaning. Swine typically ingest saliva, regurgitated food, and stool or urinary products, as well as other bodily fluids and cells during normal housing. In the second study, vaginal, cervical, uterine, oviductal, and ovarian tissues from C females on 2, 7, or 90 days after mating to T males, and penis, bulbourethral gland, urethra, testis, and epididymis tissues from C males on 2 or 7 days after mating to Tg females were collected. The presence of Tg in tissues from all C animals was tested by using PCR. We have analyzed for the presence of the Tg in various tissues [including mammary gland, salivary gland, skin (sebaceous gland), muscle, lung, liver, kidney, brain, ovary, oviduct, uterus, cervix, vagina, penis, bulbourethral gland, urethra, testis, epididymis, blood, inner and outer placental membranes and intestine]. Results indicate no presence of the Tg in tissues of C animals (n = 28) after co-habitation for 180, 220, or 250 days (n = 305 samples analyzed) or at 2 (n = 7), 7 (n = 16), or 90 (n = 6) days post-mating (n = 72, 192, or 71 samples analyzed, respectively). At Day 112 of gestation, all the samples (n = 78 samples analyzed) from nontransgenic piglets (n = 13) whose dam was aTg female were negative except for the outer placental membrane (n = 13), which screened positive for the transgene. This is not surprising because the outer placental membrane is in close contact with the uterus of the Tg dam. Finally, control piglets (n = 4) that were cross-fostered (3 days after birth) and suckled Tg dams showed no evidence of the transgene in their tissues (n = 20 samples analyzed) at weaning. The present results suggest that there is no horizontal Tg transmission between T and C pigs caused by rearing, mating, gestation, or lactation.

This project was supported by USDA BRAG Project #2005-03799.