Other
12 Authors
- Higuchi K,
- Ge F,
- Zhang H,
- Mori M,
- Guo Z,
- Zhang B,
- Tomozawa H,
- Fu X,
- Miyazaki J,
- Yan J,
- Sawashita J,
- Yao J
| First Author | Ge F | Year | 2007 |
| Journal | Lab Invest | Volume | 87 |
| Issue | 7 | Pages | 633-43 |
| PubMed ID | 17468778 | Mgi Jnum | J:122871 |
| Mgi Id | MGI:3715673 | Doi | 10.1038/labinvest.3700559 |
| Citation | Ge F, et al. (2007) Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2(c)). Lab Invest 87(7):633-43 |
| abstractText | In mice, apolipoprotein A-II (apoA-II) self-associates to form amyloid fibrils (AApoAII) in an age-associated manner. We postulated that the two most important factors in apoA-II amyloidosis are the Apoa2(c) allele, which codes for the amyloidogenic protein APOA2C (Gln5, Ala38) and transmission of amyloid fibrils. To characterize further the contribution of the Apoa2(c) allele to amyloidogenesis and improve detection of amyloidogenic materials, we established transgenic mice that overexpress APOA2C protein under the cytomegalovirus (CMV) immediate early gene (CMV-IE) enhancer/chicken beta promoter. Compared to transgene negative (Tg(-/-)) mice that express apoA-II protein mainly in the liver, mice homozygous (Tg(+/+)) and heterozygous (Tg(+/-)) for the transgene express a high level of apoA-II protein in many tissues. They also have higher plasma concentrations of apoA-II, higher ratios of ApoA-II/apolipoprotein A-I (ApoA-I) and higher concentrations of high-density lipoprotein (HDL) cholesterol. Following injection of AApoAII fibrils into Tg(+/+) mice, amyloid deposition was observed in the testis, liver, kidney, heart, lungs, spleen, tongue, stomach and intestine but not in the brain. In Tg(+/+) mice, but not in Tg(-/-) mice, amyloid deposition was induced by injection of less than 10(-8) mug AApoAII fibrils. Furthermore, deposition in Tg(+/+) mice occurred more rapidly and to a greater extent than in Tg(-/-) mice. These studies indicate that increased levels of APOA2C protein lead to earlier and greater amyloid deposition and enhanced sensitivity to the transmission of amyloid fibrils in transgenic mice. This transgenic mouse model should prove valuable for studies of amyloidosis.Laboratory Investigation (2007) 87, 633-643; doi:10.1038/labinvest.3700559; published online 30 April 2007. |
