Kim, Munkyung. Characterization of Alport syndrome and DPP9 protease using Col4a3 knock-out mice and DPP9 protease dead mutant mice. 2015, PhD Thesis, University of Basel, Faculty of Science.
Restricted to Repository staff only until 16 February 2018.
Available under License CC BY-NC-ND (Attribution-NonCommercial-NoDerivatives).
Official URL: http://edoc.unibas.ch/diss/DissB_11445
2. Dipeptidyl peptidase 9 (DPP9), an intracellular N-terminal post-proline-cleaving enzyme, is implicated in cell behavior and immune responses but its physiological function remains largely unknown. Here we investigated in vivo role of DPP9 enzyme by characterizing DPP9 knock-in mice expressing a catalytically inactive S729A mutant of DPP9 (DPP9ki/ki mice). We show that impaired suckling response is a primary cause of perinatal lethality of DPP9ki/ki mice which die within 12-18 h after birth and can be rescued by manual feeding. Suckling defect is a result of microglossia characterized by defects in the formation of intrinsic distal tongue muscle known to derive from migratory muscle progenitors while intrinsic proximal and extrinsic tongue muscles deriving from head mesenchyme develop normally in DPP9ki/ki mice. Smaller tongue size of DPP9ki/ki mice correlates with reduced number and impaired survival of migratory tongue muscle progenitors. CXCR4 mediated survival and migration of muscle progenitors is not impaired in the absence of DPP9 enzymatic activity however, an effect of DPP9 enzyme on SDF-1, ligand of CXCR4, cannot be excluded. In addition, we show that DPP9ki/ki mice exhibit impaired fetal hematopoiesis however their hematopoietic stem cells are fully competent in reconstitution of myeloid and lymphoid lineages in lethally irradiated mice. Taken together, our studies revealed for the first time that DPP9 enzyme controls survival of migratory tongue muscle progenitors and its absence in mice leads to impaired tongue development, suckling defect and neonatal lethality but DPP9 enzymatic activity in hematopoietic cells is dispensable for normal hematopoiesis.
|Committee Members:||Rüegg, Markus A. and Ksiazek, Iwona|
|Faculties and Departments:||03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Nephrologie > Exp. Transplantationsimmunologie und Nephrologie (Palmer)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||65 S.|
|Last Modified:||27 Feb 2017 15:18|
|Deposited On:||04 Dec 2015 14:32|
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