title: Comparison of hematologic, biochemical, and coagulation parameters in α1,3-galactosyltransferase gene-knockout pigs, wild-type pigs, and four primate species.
abstract: BACKGROUND
  The increasing availability of genetically engineered pigs is steadily improving the results of pig organ and cell transplantation in non-human primates (NHPs). Current techniques offer knockout of pig genes and/or knockin of human genes. Knowledge of normal values of hematologic, biochemical, coagulation, and other parameters in healthy genetically engineered pigs and NHPs is important, particularly following pig organ transplantation in NHPs. Furthermore, information on parameters in various NHP species may prove important in selecting the optimal NHP model for specific studies.
  
  
  METHODS
  We have collected hematologic, biochemical, and coagulation data on 71 α1,3-galactosyltransferase gene-knockout (GTKO) pigs, 18 GTKO pigs additionally transgenic for human CD46 (GTKO.hCD46), four GTKO.hCD46 pigs additionally transgenic for human CD55 (GTKO.hCD46.hCD55), and two GTKO.hCD46 pigs additionally transgenic for human thrombomodulin (GTKO.hCD46.hTBM).
  
  
  RESULTS
  We report these data and compare them with similar data from wild-type pigs and the three major NHP species commonly used in biomedical research (baboons, cynomolgus, and rhesus monkeys) and humans, largely from previously published reports.
  
  
  CONCLUSIONS
  Genetic modification of the pig (e.g., deletion of the Gal antigen and/or the addition of a human transgene) (i) does not result in abnormalities in hematologic, biochemical, or coagulation parameters that might impact animal welfare, (ii) seems not to alter metabolic function of vital organs, although this needs to be confirmed after their xenotransplantation, and (iii) possibly (though, by no means certainly) modifies the hematologic, biochemical, and coagulation parameters closer to human values. This study may provide a good reference for those working with genetically engineered pigs in xenotransplantation research and eventually in clinical xenotransplantation.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
authors.forename: Burcin
authors.initials: B
authors.lastname: Ekser
authors.forename: John
authors.initials: J
authors.lastname: Bianchi
authors.forename: Suyapa
authors.initials: S
authors.lastname: Ball
authors.forename: Hayato
authors.initials: H
authors.lastname: Iwase
authors.forename: Anneke
authors.initials: A
authors.lastname: Walters
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Veroux
authors.forename: Bruno
authors.initials: B
authors.lastname: Gridelli
authors.forename: Robert
authors.initials: R
authors.lastname: Wagner
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D001777:Blood Coagulation / Q000502:physiology*; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques / Q000379:methods; D005818:Genetic Engineering / Q000379:methods; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006801:Humans; D011323:Primates; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D005700:Galactosyltransferases