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Oncotarget. 2017 Jan 31;8(5):7357-7369. doi: 10.18632/oncotarget.14458.

A novel osteoporosis model with ascorbic acid deficiency in Akr1A1 gene knockout mice.

Lai CW1,2, Chen HL3, Tu MY1,4,5, Lin WY1,2, Röhrig T1,2, Yang SH6, Lan YW1,7, Chong KY7,8, Chen CM1,2,9.

Author information

Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
Department of Bioresources, Da-Yeh University, Changhua, Taiwan.
Department of Orthopaedic Surgery, Taichung Armed Forces General Hospital, Taichung, Taiwan and National Defense Medical Center, Taipei, Taiwan.
Department of Biomedical Engineering, Hungkuang University, Taichung, Taiwan.
Department of Physiology and Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan.
Rong-Hsing Translational Medicine Center, and iEGG Center, National Chung Hsing University, Taichung, Taiwan.


The AKR1A1 protein is a member of the aldo-keto reductase superfamily that is responsible for the conversion of D-glucuronate to L-gulonate in the ascorbic acid (vitamin C) synthesis pathway. In a pCAG-eGFP transgenic mouse line that was produced by pronuclear microinjection, the integration of the transgene resulted in a 30-kb genomic DNA deletion, including the Akr1A1 gene, and thus caused the knockout (KO) of the Akr1A1 gene and targeting of the eGFP gene. The Akr1A1 KO mice (Akr1A1eGFP/eGFP) exhibited insufficient serum ascorbic acid levels, abnormal bone development and osteoporosis. Using micro-CT analysis, the results showed that the microarchitecture of the 12-week-old Akr1A1eGFP/eGFP mouse femur was shorter in length and exhibited less cortical bone thickness, enlargement of the bone marrow cavity and a complete loss of the trabecular bone in the distal femur. The femoral head and neck of the proximal femur also showed a severe loss of bone mass. Based on the decreased levels of serum osteocalcin and osteoblast activity in the Akr1A1eGFP/eGFP mice, the osteoporosis might be caused by impaired bone formation. In addition, administration of ascorbic acid to the Akr1A1eGFP/eGFP mice significantly prevented the condition of osteoporotic femurs and increased bone formation. Therefore, through ascorbic acid administration, the Akr1A1 KO mice exhibited controllable osteoporosis and may serve as a novel model for osteoporotic research.


Akr1A1 gene; Pathology Section; ascorbic acid; cortical bone; knockout mice; micro-CT imaging; osteoporosis; trabecular bone

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