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

Cheng Wei Lai, Hsiao Ling Chen, Min Yu Tu, Wei Yu Lin, Theresa Röhrig, Shang Hsun Yang, Ying Wei Lan, Kowit Yu Chong, Chuan Mu Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

16 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)7357-7369
Number of pages13
JournalOncotarget
Volume8
Issue number5
DOIs
StatePublished - 2017

Keywords

  • Akr1A1 gene
  • Ascorbic acid
  • Cortical bone
  • Knockout mice
  • Micro-CT imaging
  • Osteoporosis
  • Pathology Section
  • Trabecular bone

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