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

作者：Lai Cheng Wei; Chen Hsiao Ling; Tu Min Yu; Lin Wei Yu; Rohrig Theresa; Yang Shang Hsun; Lan Ying Wei; Chong Kowit Yu^*; Chen Chuan Mu^*

来源：Oncotarget, 2017, 8(5): 7357-7369.

DOI：10.18632/oncotarget.14458

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

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 (Akr1A1(eGFP/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 Akr1A1(eGFP/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 Akr1A1(eGFP/eGFP) mice, the osteoporosis might be caused by impaired bone formation. In addition, administration of ascorbic acid to the Akr1A1(eGFP/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.

• 出版日期2017-1-31
• 单位长春大学