Dmp1-HBEGF Transgenic Mouse

RIKEN BRC October 2007
Mouse of the Month

 

Dmp1-HBEGF Transgenic Mouse
A model for osteoporosis

BRC No. 02237 C57BL/6Cr-Tg(Dmp1-HBEGF)
Research Application : Mouse models for human disease

 

A. Cortical Bone of Tibia B. Lumbar Vertebra
mn0710_0101 mn0710_0102
Wild-type
(+/+)
mn0710_0103 mn0710_0104
Hemizygote
(Tg/+)

40 days after DT injection

A. Osteocyte ablation following DT injection (8 days)
H&E staining of cortical bone of tibia
B. Development of osteoporosis following osteocyte ablation
3D images of lumbar vertebrae obtained by micro CT (Ito M, Nagasaki Univ.)

 

  Bone remodeling consists of two distinct stages, resorption and formation, which are performed by osteoclasts and osteoblasts, respectively. Dmp1-HBEGF transgenic mice express human HB-EGF as the receptor for diphtheria toxin (DT) on the cell surface of osteocytes under the control of Dmp1 promoter. Most of the osteocytes (70 to 80%) can be ablated in these transgenic mice by injection of DT. The osteocytes-ablated mice develop osteoporosis, even in young age, showing fragile bone with intracortical porosity and microfractures, osteoblastic dysfunction, and loss of trabecular bone with microstructural deterioration and adipose tissue proliferation in the marrow space. Interestingly, the mice do not respond to mechanical unloading with bone loss. This strain is a useful model for the study of osteoprosis and mechanotransduction in bone.

 

Depositor :  Dr. Kyoji Ikeda (National Center for Geriatrics & Gerontology)
Reference :  Cell Metab. (2007) 5(6):464-75.


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