| Autor: |
Touchette EK; Inotiv, St. Louis, Missouri;, Email: etouchette@inotivco.com., Bates MC; Inotiv, St. Louis, Missouri., Johnson MC; Inotiv, St. Louis, Missouri., O'Brien TC; Inotiv, St. Louis, Missouri., Melton RJ; Inotiv, St. Louis, Missouri., Long KR; Inotiv, St. Louis, Missouri., Kakuni M; PhoenixBio Co., Ltd., Kagamiyama, Hiroshima, Japan ; KMT Hepatech Inc., Edmonton, Alberta, Canada., Baginski M; PhoenixBio USA Corporation, New York., Radiloff DR; PhoenixBio USA Corporation, New York., Sagartz JE; Inotiv, St. Louis, Missouri. |
| Abstrakt: |
Humanized liver chimeric mice (PXB-mice) are generated by the transplantation of human hepatocytes into mice that have severe combined immunodeficiency and express an albumin-promoted urokinase-type plasminogen activator (cDNA-uPA/SCID) transgene. Human hepatocytes cannot synthesize ascorbic acid (AA; commonly called vitamin C) and humans require supplementation to prevent vitamin C deficiency. PXB-mouse livers contain up to approximately 95% human hepatocytes, which likely affects AA synthesis. To determine whether dietary AA supplementation prevents scurvy-like symptoms and death in PXB-mice, a 12 week study that compared nonsupplemented and supplemented PXB-mice was conducted. Approximately 4 weeks into the study, PXB-mice without dietary supplementation of AA displayed weight loss and clinical signs of hypovitaminosis C, including hunched posture, unkempt appearance, and lameness. Pathologic evaluation of nonsupplemented PXB-mice revealed lesions consistent with hypovitaminosis C. Mean serum AA concentrations in the nonsupplemented PXB-mice were below the limit of quantitation (0.5 μg/mL) and were substantially less than those of controls. AA was also measured in a number of tissues, including adrenal gland, brain, liver, and testis; low AA concentrations were similarly observed in tissues obtained from the nonsupplemented PXB-mice. Collectively, these findings support AA supplementation in PXB-mice to prevent the development of hypovitaminosis C and the potential utility of nonsupplemented PXB-mice as an animal model of scurvy. |
