| First Author | Liu L | Year | 2017 |
| Journal | Lab Invest | Volume | 97 |
| Issue | 4 | Pages | 395-408 |
| PubMed ID | 28134916 | Mgi Jnum | J:260682 |
| Mgi Id | MGI:6152574 | Doi | 10.1038/labinvest.2016.156 |
| Citation | Liu L, et al. (2017) Rescue of retinal morphology and function in a humanized mouse at the mouse retinol-binding protein locus. Lab Invest 97(4):395-408 |
| abstractText | Retinol-binding protein RBP4 is the specific carrier for retinol in the blood. We previously produced a Rbp4-deficient (Rbp4(-/-)) mouse that showed electroretinogram (ERG) abnormalities, accompanied by histological and electron-microscopic changes such as fewer synapses in the inner plexiform layer in the central retina. To address whether human RBP4 gene expression can rescue the phenotypes observed in Rbp4(-/-) mice, we produced a humanized (Rbp4(hRBP4orf/ hRBP4orf)) mouse with a human RBP4 open reading frame in the mouse Rbp4 locus using a Cre-mutant lox recombination system. In Rbp4(hRBP4orf/hRBP4orf) mice, the tissue-specific expression pattern of hRBP4orf was roughly the same as that of mouse Rbp4. ERG and morphological abnormalities observed in Rbp4(-/-) mice were rescued in Rbp4(hRBP4orf/hRBP4orf) mice as early as 7 weeks of age. The temporal expression pattern of hRBP4orf in the liver of Rbp4(hRBP4orf/hRBP4orf) mice was similar to that of mouse Rbp4 in Rbp4(+/+)mice. In contrast, hRBP4orf expression levels in eyes were significantly lower at 6 and 12 weeks of age compared with mouse Rbp4 but were restored to the control levels at 24 weeks. The serum hRBP4 levels in Rbp4(hRBP4orf/hRBP4orf) mice were approximately 30% of those in Rbp4(+/+) at all ages examined. In accordance with this finding, the plasma retinol levels remained low in Rbp4(hRBP4orf/hRBP4orf) mice. Retinol accumulation in the liver occurred in control and Rbp4(hRBP4orf/hRBP4orf) mice but was higher in Rbp4(hRBP4orf/hRBP4orf) mice at 30 weeks of age. Mouse transthyretin expression was not altered in Rbp4(-/-) or Rbp4(hRBP4orf/hRBP4orf) mice. Taken together, 30% of the serum RBP4 level was sufficient to correct the abnormal phenotypes observed in Rbp4(-/-) mice. |
