Assessing unintended effects of a mammary-specific transgene at the whole animal level in host and non-target animals.
Risk assessment in transgenic plants is intrinsically different than that for transgenic animals; however both require the verification of proper transgene function and in conjunction, an estimate of any unintended effects caused by expression of the transgene. This work was designed to gather data regarding methodologies to detect pleiotropic effects at the whole animal level using a line of transgenic goats that produce the antimicrobial protein human lysozyme (hLZ) in their milk with the goal of using the milk to treat childhood diarrhea. Metabolomics was used to determine the serum metabolite profile of both the host (lactating does) and non-target organism (kid goats raised on control or hLZ milk) prior to weaning (60 days), at weaning (90 days) and 1 month post-weaning (120 days). In addition, intestinal histology of the kid goats was also carried out. Histological analysis of intestinal segments of the pre-weaning group revealed significantly wider duodenal villi (p = 0.014) and significantly longer villi (p = 0.028) and deeper crypts (p = 0.030) in the ileum of kid goats consuming hLZ milk. Serum metabolomics was capable of detecting differences over time but revealed no significant differences in metabolites between control and hLZ fed kids after correction for false discovery rate. Serum metabolomics of control or hLZ lactating does showed only one significant difference in an unknown metabolite (q = 0.0422). The results as a whole indicate that consumption of hLZ milk results in positive or insignificant intestinal morphology and metabolic changes. This work contributes to the establishment of the safety and durability of the hLZ mammary-specific transgene.
Department of Animal Science, University of California, Davis, One Shields Ave, Davis, CA, 95616, USA.
Merritt
M
Clark
James D
JD
Murray
Elizabeth A
EA
Maga
D000818:Animals; D030801:Animals, Genetically Modified; D005260:Female; D018014:Gene Transfer Techniques / Q000009:adverse effects*; D006041:Goats / Q000097:blood / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D007774:Lactation / Q000502:physiology*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008892:Milk / Q000201:enzymology*; D009113:Muramidase / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment
D009113:Muramidase