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Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues

Al-Jazzar, A; Javaheri, B; Prideaux, M; Boyde, A; Scudamore, C L; Cherifi, C; Hay, E; Hopkinson, M; Boyd, M; Cohen-Solal, M; Farquharson, C; Pitsillides, A A


A Al-Jazzar

B Javaheri

M Prideaux

A Boyde

C L Scudamore

C Cherifi

E Hay

M Hopkinson

M Boyd

M Cohen-Solal

C Farquharson

A A Pitsillides


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.


Al-Jazzar, A., Javaheri, B., Prideaux, M., Boyde, A., Scudamore, C. L., Cherifi, C., …Pitsillides, A. A. (2017). Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues. International Journal of Molecular Sciences, 18(1),

Journal Article Type Article
Acceptance Date Dec 15, 2016
Publication Date Jan 1, 2017
Deposit Date Apr 8, 2017
Publicly Available Date Apr 8, 2017
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 18
Issue 1
Public URL


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