Structure and expression of the mouse homologue of the XK gene

Collec, Emmanuel; Colin, Yves; Carbonnet, Florence; Hattab, Claude; Bertrand, Olivier; Cartron, Jean Pierre; Kim, C. Le Van

doi:10.1007/s002510050681

Cited by 13 publications

(9 citation statements)

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“…In fact, genetic deletion of the XK gene in humans (McLeod syndrome) leads to extreme depression of antigens carried by the Kell glycoprotein. 19 Mice have an ortholog of the human XK gene, 20 which has 82% identity at the amino acid level, including the cysteine at Position 347, which in the human XK forms a disulfide bond with human Kell Cysteine 72. Given the posttransfusion stability of the described KEL1 and KEL2 murine RBCs, it is possible that the transgenes are forming heterodimers with the murine XK ortholog; however, this remains untested.…”

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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“…Mouse Xk protein has 82% amino acid similarity with human XK and is also linked to the mouse Kell protein. The mouse Xk gene is organized into three exons with differences in expression pattern when compared to the human gene [4; 5]. The transport substrate for XK protein is still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Human Kell is a highly polymorphic, type II glycoprotein [3; 4; 6] that is mainly expressed in erythroid tissue but is also observed in human non-erythroid tissues including skeletal muscle, heart and brain [1; 7; 8; 9]. Mouse Kell has 74% amino acid similarity with human Kell and has ECE-3 activity [10].…”

Section: Introductionmentioning

confidence: 99%

Ablation of the Kell/Xk complex alters erythrocyte divalent cation homeostasis

Rivera

Kam

et al. 2013

Blood Cells, Molecules, and Diseases

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XK is a putative transporter of unknown function that is ubiquitously expressed and linked through disulfide bonds to Kell protein, an endothelin-3 (ET-3)-converting enzyme. We generated three knockout (KO) mice that lacked either Xk, Kell or both proteins and characterized erythrocyte cation levels, transport and hematological parameters. Absence of Xk or Kell was accompanied by changes in erythrocyte K+, Mg2+, Na+ and Ca2+ transport that were associated with changes in mean cellular volume and corpuscular hemoglobin concentration mean. Baseline Ca2+-ATPase activity was undetected in erythrocytes from all three mouse types but was restored upon pre-incubation with ET-3. Consistent with these alterations in Ca2+ handling, we observed increased Gardos channel activity in Kel and Xk KO mice. In addition Kel deletion was associated with increased Mg2+ permeability while Xk deletion blocked Na/Mg exchanger activity. Our results provide evidence that cellular divalent cation regulation is functionally coupled to the Kell/XK system in erythrocytes and loss of this complex may contribute to acanthocytosis formation in McLeod syndrome.

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“…The recent identification of the XK homologue in the mouse 46 should facilitate the description of its expression in specific brain areas as well as the search for possible interactions with transmitter peptides of the striatum.…”

Section: Discussionmentioning

confidence: 99%

The chorea of McLeod syndrome

et al. 2001

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Among the movement disorders associated with acanthocytosis, McLeod syndrome (McKusick 314850) is the one that is best characterized on the molecular level. Its defining feature is low reactivity of Kell erythrocyte antigens. This is due to absence of membrane protein KX that forms a complex with the Kell protein. KX is coded for by the XK gene on the X-chromosome. We present six males (aged 29 to 60 years), with proven XK mutations, to discuss the chorea associated with McLeod syndrome. The movement disorder commonly develops in the fifth decade and is progressive. It affects the limbs, the trunk and the face. In addition to facial grimacing, involuntary vocalization can be present. In early stages there may only be some restlessness or slight involuntary distal movements of ankles and fingers. Lip-biting and facial tics seem more common in autosomal recessive choreoacanthocytosis linked to chromosome 9. This, together with the absence of dysphagia in McLeod syndrome, may help in differential diagnosis. Recent findings suggest a role for the endothelin system of the striatum in the pathogenesis of McLeod syndrome.

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Structure and expression of the mouse homologue of the XK gene

Cited by 13 publications

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

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

Ablation of the Kell/Xk complex alters erythrocyte divalent cation homeostasis

The chorea of McLeod syndrome

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