title: A novel osteoporosis model with ascorbic acid deficiency in Akr1A1 gene knockout mice.
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.
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.|Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Lai
authors.affiliation: Department of Bioresources, Da-Yeh University, Changhua, Taiwan.
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, 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.
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Tu
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.|Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Lin
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.|Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Theresa
authors.initials: T
authors.lastname: Röhrig
authors.affiliation: Department of Physiology and Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shang-Hsun
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.|Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Ying-Wei
authors.initials: YW
authors.lastname: Lan
authors.affiliation: 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.
authors.forename: Kowit-Yu
authors.initials: KY
authors.lastname: Chong
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.|Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.|Rong-Hsing Translational Medicine Center, and iEGG Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chuan-Mu
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000449:Aldehyde Reductase / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000097:blood; D001206:Ascorbic Acid Deficiency / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology*; D055786:Gene Knockout Techniques; D020022:Genetic Predisposition to Disease; D018345:Mice, Knockout; D010006:Osteoblasts / Q000201:enzymology / Q000473:pathology; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis; D010024:Osteoporosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D010641:Phenotype; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D015675:Osteocalcin; D000449:Aldehyde Reductase; D001205:Ascorbic Acid
keywords: Akr1A1 gene; Pathology Section; ascorbic acid; cortical bone; knockout mice; micro-CT imaging; osteoporosis; trabecular bone