Pietzner, J. and Baer, P. C. and Duecker, R. P. and Merscher, M. B. and Satzger-Prodinger, C. and Bechmann, I. and Wietelmann, A. and Del Turco, D. and Doering, C. and Kuci, S. and Bader, P. and Schirmer, S. and Zielen, S. and Schubert, R. (2013) Bone marrow transplantation improves the outcome of Atm-deficient mice through the migration of ATM-competent cells. HUMAN MOLECULAR GENETICS, 22 (3). pp. 493-507. ISSN 0964-6906, 1460-2083
Full text not available from this repository. (Request a copy)Abstract
Ataxia telangiectasia (A-T) is a highly pleiotropic disorder. Patients suffer from progressive neurodegeneration, severe bronchial complications, immunodeficiency, hypersensitivity to radiotherapy and elevated risk of malignancies. Leukemia and lymphoma, along with lung failure, are the main causes of morbidity and mortality in A-T patients. At present, no effective therapy for A-T exists. One promising therapeutic approach is bone marrow transplantation (BMT) that is already used as a curative therapy for other genomic instability syndromes. We used an established clinically relevant non-myeloablative host-conditioning regimen and transplanted green fluorescent protein (GFP)-expressing ataxia telangiectasia mutated (ATM)-competent bone marrow-derived cells (BMDCs) into Atm-deficient mice. GFP expression allowed tracking of the potential migration of the cells into the tissues of recipient animals. Donor BMDCs migrated into the bone marrow, blood, thymus, spleen and lung tissue of Atm-deficient mice showing an ATM-competent phenotype. BMT inhibited thymic lymphomas, normalized T-lymphocyte populations, improved weight gain and rearing activity of Atm-deficient mice. In contrast, no GFP cells were found in the cerebellum or cerebrum, and we detected decreased size index in MRI imaging of the cerebellum in 8-month-old transplanted Atm-deficient mice in comparison to wild-type mice. The repopulation with ATM-competent BMDCs is associated with a prolonged lifespan and significantly improved the phenotype of Atm-deficient mice.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PREMATURE TERMINATION CODONS; ATAXIA-TELANGIECTASIA GENE; ACUTE LUNG INJURY; PULMONARY-DISEASE; PURKINJE NEURONS; MUTANT MICE; DNA-DAMAGE; STEM-CELLS; ANTIOXIDANT; KINASE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Apr 2020 09:29 |
| Last Modified: | 28 Apr 2020 09:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17251 |
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