Jung
Fakultäten » Medizinische Fakultät » Neurologie, Klinik für » PD Dr. Hans H. Jung » Jung
Completed research project
| Title / Titel | A C. elegans nematode model of the human McLeod syndrome | ||||||
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| Abstract (PDF, 14 KB) | |||||||
| Summary / Zusammenfassung | The X-linked McLeod blood group phenotype is characterized by absent Kx erythrocyte antigen and weak Kell antigens. Male carriers of the McLeod blood group phenotype are prone to develop a multi-system disorder with hematological, neuromuscular, and central nervous system manifestations, assigned as the McLeod neuroacanthocytosis syndrome. McLeod syndrome is caused by mutations of the XK gene, encoding the XK protein, a putative membrane transport protein with 10 trans-membrane domains. Up to date, the physiological function of the XK protein is not known. However, the ced-8 gene in the nematode C. elegans has strong similarities to the human XK gene. Loss-of-function mutations in ced-8 alter the timing of the embryonic programmed cell death. These data indicate a possible role of apoptosis dysregulation in the pathogenesis of striatal neurodegeneration and myopathy in McLeod syndrome. With our study, we intend to construct a nematode model of the human McLeod syndrome in order to elucidate the disease mechanisms. First, we want to investigate a possible functional homology between ced-8 and XK by inserting the human wild-type XK gene into ced-8 deficient mutants. Functional homology would be presumed in the case of reversal of the impaired function in the transgenic nematodes. In the case of a working model system, the next experimental steps would include the expression of different disease-causing XK mutations, and the search for any resulting changes in the pattern of embryonic programmed cell death. These investigations would help to elucidate the pathogenesis of the XK dysfunction in human McLeod syndrome, and could potentially allow the development of a model to investigate possible preventive and/or therapeutic interventions. | ||||||
| Publications / Publikationen | Walker RH, Jung HH, Dobson-Stone C, Rampoldi L, Sano A, Tison F, Danek A (2007) Neurologic phenotypes associated with acanthocytosis. Neurology; 68:92-98.Dydak U, Mueller S, Sandor PS, Meier D, Boesiger P, Jung HH (2006) Cerebral metabolic alterations in McLeod syndrome. Eur Neurol; 56:17-23.Walker RH, Jung HH, Tison F, Lee S, Danek A (2007) Phenotypic variation among brothers with the McLeod neuroacanthocytosis syndrome. Mov Disord; 22: 244-247.Danek A, Jung HH, Landwehrmeyer B, Melone MAB, Rampoldi L, Broccoli V, Walker RH (2005) Neuroacanthocytosis: new developments in a neglected group of dementing disorders. J Neurol Sci; 15:229-230.Jung HH, Danek A, Dobson-Stone C, Redman C (2004) McLeod Neuroacanthocytosis Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2004. Available at http://www.genetests.orgJung HH, Haker H (2004) Schizophrenia as a manifestation of X-linked McLeod-neuroacanthocytosis syndrome. J Clin Psychiatry; 65: 722-723Jung HH, Hergersberg M, Vogt M, Pahnke J, Treyer V, Röthlisberger B, Kollias SS, Russo D, Frey BM (2003) McLeod phenotype associated with a XK missense mutation without hematological, neuromuscular, or cerebral involvement. Transfusion; 43: 928-938Jung HH, Brandner S (2002) Malignant McLeod myopathy. Muscle Nerve; 26: 424-427Jung HH, Russo D, Redman C, Brandner S (2001) Kell and XK immunohistochemistry in McLeod myopathy. Muscle Nerve 24: 1346-1351Jung HH, Hergersberg M, Kneifel S, Alkadhi H, Schiess R, Weigell-Weber M, Daniels G, Kollias S, Hess K (2001) McLeod Syndrome: A novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings. Ann Neurol 49: 384-392. | ||||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Foundation Synapsis Foundation, Betty and David Koetser Foundation for Brain Research, Mutaxia Foundation |
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| Duration of Project / Projektdauer | Jan 2004 to Dec 2008 |