Reference - Detail
| RRC ID | 87211 |
|---|---|
| Author | Al-Jazzar A, Javaheri B, Prideaux M, Boyde A, Scudamore CL, Cherifi C, Hay E, Hopkinson M, Boyd M, Cohen-Solal M, Farquharson C, Pitsillides AA. |
| Title | Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues. |
| Journal | Int J Mol Sci |
| Abstract |
Mice harbouring a dentin matrix protein 1 (Dmp1) promoter-driven human diphtheria toxin (DT) receptor (HDTR) transgene (Tg) have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT) treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT) littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2), was also found in many non-skeletal tissues in Tg mice; indicative of direct "off-target" DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone. |
| Volume | 18(1) |
| Published | 2016-12-26 |
| DOI | 10.3390/ijms18010029 |
| PII | ijms18010029 |
| PMID | 28035954 |
| PMC | PMC5297664 |
| MeSH | Animals Bone and Bones / metabolism Brain / metabolism Diphtheria Toxin / toxicity Extracellular Matrix Proteins / genetics* Heparin-binding EGF-like Growth Factor / genetics* Heparin-binding EGF-like Growth Factor / metabolism Humans Kidney / metabolism Mice Myocardium / metabolism Organ Specificity Osteocytes / drug effects Osteocytes / metabolism Peptide Elongation Factor 2 / metabolism Promoter Regions, Genetic Transgenes* |
| IF | 4.556 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC02237 |