A mouse model for studying the effect of Erythropoietin overexpression in Apolipoprotein E knockout mice

作者：Schober S; Tebb G; Gille L; Thiersch M; Ruelicke T

来源：Wiener Tierarztliche Monatsschrift, 2016, 103(3-4): 68-78.

• erythropoietin
• apolipoprotein E
• oxidative stress
• mouse model
• transgenic mice

Erythropoietin (Epo) is the main hormone that promotes erythropoiesis. Its recombinant form (rHuEpo) and its derivatives (epoetins) are potent drugs widely used in the treatment of anaemia. Despite the routine use of Epo, the adverse events have not been clearly defined, although there are reports linking its use to cardiovascular disease. To investigate the effects of high levels of Epo in patients prone to cardiovascular disease, we have generated a new double-mutant mouse model Apoe(-/-); Tg(EPO) by crossing the human Epo-overexpressing Tg(EPO) mouse with an apolipoprotein E knockout (Apoe(-/-)) mouse, a model used in the study of cardiovascular diseases. Blood parameters, body weight and life expectancy were analysed. The sulfhydryl (SH) group concentration in whole blood and the levels of haemoglobin-nitric oxide (HbNO) complexes in erythrocyte pellets were investigated as indicators for oxidative stress. The findings are compared to the parameters in single mutant and wild-type mice. Double-mutant mice overexpressing Epo have the same haemoglobin and haematocrit levels as the Epo-overexpressing single mutant. Mice overexpressing Epo have an increased concentration of SH groups in the blood, while male Apoe knockout mice show significantly more HbNO complexes in erythrocyte pellets than Apoe(-/-); Tg(EPO) double-mutant mice. Unfortunately, the double mutants have a severely reduced life expectancy and splenectomy was necessary to enable certain experimental procedures. Because of animal welfare considerations, the model is not recommended for routine studies.

• 出版日期2016