Onset of expression of the components of the Kell blood group complex

Pu, Jeffrey J.; Redman, Colvin M.; Visser, J. W. M.; Lee, Soohee

doi:10.1111/j.1537-2995.2005.04289.x

Cited by 14 publications

(15 citation statements)

References 28 publications

(38 reference statements)

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“…As is seen with human Kell antigens, expression is detected in early erythropoiesis. 18 Expression of the transgene does not alter the fine morphology or circulatory life span of RBCs, with the KEL1 and KEL2 transgenes being stably expressed and with the animals having normal hematologic variables. In aggregate, these findings demonstrate a new murine system with mice expressing human Kell glycoprotein variants that differ by a single amino acid.…”

Section: Discussionmentioning

confidence: 99%

Generation of transgenic mice with antithetical KEL1 and KEL2 human blood group antigens on red blood cells

et al. 2012

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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. STUDY DESIGN AND 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. CONCLUSION 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.

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Section: Discussionmentioning

confidence: 99%

Generation of transgenic mice with antithetical KEL1 and KEL2 human blood group antigens on red blood cells

et al. 2012

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“…In the mouse Kell and Xk, the amino acids implicated in the interaction are conserved. Furthermore, Kell expression independent of Xk has been observed in different systems . Fy is a multipass transmembrane protein.…”

Section: Challengesmentioning

confidence: 99%

Generation of mice expressing human RHAG and RHD blood group genes

Goossens

2015

ISBT Science Series

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Anti‐RhD prophylaxis of haemolytic disease of the fetus and newborn (HDFN) is highly effective, but since the suppressive mechanism remains uncertain, a mouse model of this pathology would be useful to achieve a better understanding of the processes involved. A number of highly interesting models of mice transgenic for human blood groups, producing alloantibodies through transfusion, and even pregnancy, have been developed in recent years. Expression of RhD has, however, proved difficult in mice, due to its integration into a membrane complex, a heterotrimer involving not only Rh, but also its RhAG protein partner. In our experience, RhD could be expressed from a human RHD gene on a BAC or from RHD cDNA under control of β‐globin regulatory elements, but RhD erythrocyte membrane expression was obtained only in mice transgenic for both the RHAG and RHD human genes. We here give an overview of our approach to the generation of transgenic mice co‐expressing human RhAG and RhD erythrocyte membrane proteins, and discuss further challenges to be resolved in the quest for a model of RhD alloimmunisation and HDFN.

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“…Unlike RhD sensitization, fetal anemia caused by antibodies to Kell are not primarily the result of hemolysis but are mainly the result of inhibition of erythropoiesis. 25 The Kell glycoprotein is expressed in early erythroid progenitor cells, 26,27 and anti-KEL1-related fetal anemia is likely caused by promoting the immune destruction of K-positive RBCs, by macrophages, at an early progenitor cell stage. 28 Because the procedure for collecting fetal blood is risky and serologic tests to predict a fetus at risk for HDN are unreliable, genotyping methods for KEL*1 and KEL*2 using fetal DNA from amniocytes have been developed based on PCR BsmI-RFLP analysis or allele-specific PCR.…”

Section: Fetal and Newborn Anemia Related To Anti-kmentioning

confidence: 99%