Changes in red cell ion transport, reduced intratumoral neovascularization, and some mild motor function abnormalities accompany targeted disruption of the Mouse Kell gene (Kel).

Abstract

Kell (ECE-3), a highly polymorphic blood group glycoprotein, displays more than 30 antigens that produce allo-antibodies and, on red blood cells (RBCs), is complexed through a single disulfide bond with the integral membrane protein, XK. XK is a putative membrane transporter whose absence results in a late onset form of neuromuscular abnormalities known as the McLeod syndrome. Although Kell glycoprotein is known to be an endothelin-3-converting enzyme, the full extent of its physiological function is unknown. To study the functions of Kell glycoprotein, we undertook targeted disruption of the murine Kel gene by homologous recombination. RBCs from Kel(-/-) mice lacked Kell glycoprotein, Kell/XK complex, and endothelin-3-converting enzyme activity and had reduced levels of XK. XK mRNA levels in spleen, brain, and testis were unchanged. In Kel(-/-) mice RBC Gardos channel activity was increased and the normal enhancement by endothelin-3 was blunted. Analysis of the microvessels of tumors produced from LL2 cells indicated that the central portion of tumors from wild-type mice were populated with many mature blood vessels, but that vessels in tumors from Kel(-/-) mice were fewer and smaller. The absence of Kell glycoprotein mildly affected some motor activities identified by foot splay on the drop tests. The targeted disruption of Kel in mouse enabled us to identify phenotypes that would not be easily detected in humans lacking Kell glycoprotein. In this regard, the Kell knockout mouse provides a good animal model for the study of normal and/or pathophysiological functions of Kell glycoprotein.

• Authors: Xiang Zhu, Alicia Rivera, Mari S Golub, Jianbin Peng, Quan Sha, Xu Wu, Xiaoling Song, Prem Kumarathasan, Mac Ho, Colvin M Redman, Soohee Lee
• Journal: American journal of hematology (Am J Hematol) Vol. 84 Issue 8 Pg. 492-8 (Aug 2009) ISSN: 1096-8652 [Electronic] United States
• PMID: 19544475 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Kell Blood-Group System
• RNA, Messenger
• Aspartic Acid Endopeptidases
• Metalloendopeptidases
• Endothelin-Converting Enzymes

Topics

• Animals
• Aspartic Acid Endopeptidases (genetics, metabolism)
• Carcinoma, Lewis Lung (genetics, metabolism, pathology)
• Endothelin-Converting Enzymes
• Erythrocytes (metabolism)
• Gene Knockout Techniques
• Ion Transport (genetics)
• Kell Blood-Group System (genetics, metabolism)
• Metalloendopeptidases (genetics, metabolism)
• Mice
• Mice, Knockout
• Motor Activity
• Neovascularization, Pathologic (genetics, metabolism, pathology)
• Organ Specificity
• RNA, Messenger (biosynthesis)