Human CD46 transgene inhibits deposition of human complements in transgenic murine heart xenograft
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ORGAN TRANSPLANTATION
- Issue:
- 11
- DOI:
- 10.3760/cma.j.issn.0254-1785.2008.11.001
- Key Word:
- 转基因;移植,异种;补体;小鼠;Transgenes;Transplantation,heterologous;Complement;Mice
Abstract： Objective To investigate the inhibition of human complements deposition by human CD46 expression on transgenic mouse hearts.Methods The whole length cDNA encoding human CD46 was amplified by PCR using human cDNA library.The human CD46 gene was introduced into fertilized mice eggs by microinjection to produce transgenic mice expressing human CD46.Isolated hearts from two groups of mice(wild type and hCD46-expressing)were perfused ex vivo with 10% pooled human plasma by modified Langendorff profusion system.Heart function was evaluated by mean heart beating time.Deposition of complements C3c and C9 in the perfused muffne hearts was examined by immunofluorescence and immunohistochemistry respectively.Results Mean heart beating time was prolonged to 42.6±20.6 min in the hCD46 expression group(P＜0.01)in contrast to 20.2 ±12.5 min in the wild type group.The expression of hCD46 in transgenic mice was detected by RTPCR analysis.In immunohistological examination,hCD46-expressing hearts exhibited a reduction in deposition of complements C9 and C3 compared with nontransgenic mouse hearts.Conclusion Human CD46 transgenic mice have been obtained by microinjection.Expression of human CD46 gene in xenografts could inhibit deposition of human complements C3c and C9.
- [1]杨春荣,马霄飞,李吉霞,等.PMSG不同剂量对小鼠超排效果的影响[J].2001,(6).
- [2]李子义,谭景和,孙兴参,等.不同激素剂量对幼鼠超数排卵及超排卵质量的影响[J].1999,(3).
- [3]A G, Rose,D K, Cooper,P A, Human,etc.Histopathology of hyperacute rejection of the heart: experimental and clinical observations in allografts and xenografts.[J].1900,10(2).
- [4]J P, Lindemann,H R, Besch,A M, Watanabe.Indirect and direct effects of the divalent cation ionophore A23187 on guinea pig and rat ventricular myocardium.[J].1979,44(4).
- [5]J L, Platt,F H, Bach.The barrier to xenotransplantation.[J].1991,52(6).
- [6]DALMASSO AGUSTIN P.,VERCELLOTTI GREGORY M.,PLATT JEFFREY L.,etc.Inhibition of Complement-Mediated Endothelial Cell Cytotoxicity by Decay-Accelerating Factor[J].1991.
- [7]J L, Platt,G M, Vercellotti,A P, Dalmasso,etc.Transplantation of discordant xenografts: a review of progress.[J].1990,11(12).
- [8]Cowan PJ,Tange MJ,Aminian A,etc.High-level endothelial expression of human CD59 prolongs heart function in an ex vivo model of xenograft rejection.[J].1998,65(6).
- [9]Richards A,Parsons N,Carrington C,etc.Transgenic pigs expressing human CD59, in combination with human membrane cofactor protein and human decay-accelerating factor.[J].2005,12(2).
- [10]Z, Ahmad,F J, Green,H S, Subuhi,etc.Autonomic regulation of type 1 protein phosphatase in cardiac muscle.[J].1989,264(7).
- [11]T J, Kroshus,R M, Bolman,A P, Dalmasso,etc.Expression of human CD59 in transgenic pig organs enhances organ survival in an ex vivo xenogeneic perfusion model.[J].1996,61(10).
- [12]Bjorkland A,Korsgren O,White DJ,etc.Expression of complement regulatory proteins on islets of Langerhans: a comparison between human islets and islets isolated from normal and hDAF transgenic pigs.[J].2001,72(2).
- [13]Fodor WL,Pizzolato MC.An engineered bifunctional recombinant molecule that regulates humoral and cellular effector functions of the immune system.[J].2003,75(4).
- [14]A P, Dalmasso,G M, Vercellotti,R J, Fischel,etc.Mechanism of complement activation in the hyperacute rejection of porcine organs transplanted into primate recipients.[J].1992,140(5).
- [15]田小利.转基因动物原理、技术与应用[M].1995.