title: Generation of transgenic mice with antithetical KEL1 and KEL2 human blood group antigens on red blood cells.
abstract: BACKGROUND
  KEL1, also known as "K", is one of the most immunogenic red blood cell (RBC) antigens. KEL2, also known as "k," differs from KEL1 by a single amino acid. Anti-Kell system antibodies can lead to significant adverse clinical outcomes in humans, including hemolytic complications in alloimmunized transfusion recipients or in infants of alloimmunized mothers. To provide a platform for in-depth immunologic studies of alloimmunization and subsequent sequelae, we generated transgenic mice expressing the human KEL1 or KEL2 antigens.
  
  
  METHODS
  Vectors were created in which cDNAs encoding either KEL1 or KEL2 were regulated by an erythroid specific β-globin promoter and enhancer. Pronuclear microinjections were carried out into a C57BL6 background, and founder pups were identified by polymerase chain reaction and screened for expression by flow cytometry. RBC life span and antigen stability were assessed by dye labeling RBCs, transfusing into agammaglobulinemic (µMT) recipients, and tracking by flow cytometry.
  
  
  RESULTS
  The expression of either KEL1 or KEL2 is RBC specific and first occurs on early RBC precursors. Both KEL1 and KEL2 RBCs have a normal circulatory life span and stable antigen expression. Expression of KEL1 or KEL2 does not result in altered levels of murine Kell, and resulting RBCs have normal hematologic variables.
  
  
  CONCLUSIONS
  The KEL1 and KEL2 mice represent the first murine system of RBC immunity with antithetical antigens, allowing a more precise modeling of human RBC immunology in general and also a platform for development of novel therapeutics to prevent or minimize the dangers of RBC alloimmunization to the KEL1 and KEL2 antigens in particular.
authors.affiliation: Department of Pathology and Laboratory Medicine, Aflac Cancer Center and Blood Disorders Service, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Smith
authors.forename: Kate L
authors.initials: KL
authors.lastname: Henry
authors.forename: Chantel M
authors.initials: CM
authors.lastname: Cadwell
authors.forename: Ashley
authors.initials: A
authors.lastname: Bennett
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Hendrickson
authors.forename: Tom
authors.initials: T
authors.lastname: Frame
authors.forename: James C
authors.initials: JC
authors.lastname: Zimring
mesh_terms: D000818:Animals; D001803:Blood Transfusion; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D004912:Erythrocytes / Q000166:cytology / Q000276:immunology*; D015723:Gene Library; D006801:Humans; D007626:Kell Blood-Group System / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D019076:Transgenes / Q000235:genetics
chemical_list: D000939:Epitopes; D007626:Kell Blood-Group System