Ong G L, Mattes M J
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
J Immunol Methods. 1989 Dec 20;125(1-2):147-58. doi: 10.1016/0022-1759(89)90088-4.
Common laboratory mouse strains have very low complement levels relative to humans, rats, guinea pigs, rabbits and other mammals, which limits the value of the mouse as an experimental model. We therefore tested serum complement levels of 43 mouse strains and 11 rat strains, for the purpose of selecting a convenient laboratory animal having high complement levels. Total complement activity was determined with both erythrocytes and human tumor cells as targets. Eight mouse strains were identified that have complement levels comparable to those of other mammals. These mouse sera lyse tumor cell targets as well as sera from humans, rats or guinea pigs, although they are somewhat less active than rabbit sera. They are relatively inefficient in lysing erythrocyte targets, yet are as active as rabbit serum in this assay. Target cell lysis was demonstrated to be via the classical pathway of complement activation. Of the eight 'high complement' mouse strains, four were recently derived from wild mice, and one, SF/CamEi, was derived from wild mice in 1951. The three other strains, BUB/BnJ, DA/HuSn and RIIIS/J, were developed more than 40 years ago, but apparently were not tested previously for complement activity. Using the BUB mouse as a representative of the 'high complement' mice, we assayed levels of the nine complement components, in an attempt to identify the cause of high complement activity. No difference in levels of C1, C2, C4, C8 or C9 was detected between BUB and BDF1 mice. C2 activity was very low in both strains. C3, C5, C6 and C7 activities were higher in BUB mice than in BDF1 mice, indicating that variation in these complement components is responsible for the difference in total complement activity. The genes determining the 'high complement' phenotype appeared to be semi-dominant in F1 hybrids. The 'high-complement' mouse strains, and recombinant strains derived from them, will be useful in a wide range of biomedical research.
与人类、大鼠、豚鼠、兔子和其他哺乳动物相比，常见的实验室小鼠品系的补体水平非常低，这限制了小鼠作为实验模型的价值。因此，我们检测了43个小鼠品系和11个大鼠品系的血清补体水平，目的是选择一种补体水平高的便利实验动物。以红细胞和人肿瘤细胞为靶标测定总补体活性。鉴定出8个小鼠品系，其补体水平与其他哺乳动物相当。这些小鼠血清裂解肿瘤细胞靶标的能力与人、大鼠或豚鼠的血清相当，尽管其活性略低于兔血清。它们在裂解红细胞靶标方面效率相对较低，但在该测定中与兔血清活性相当。已证明靶细胞裂解是通过补体激活的经典途径进行的。在这8个“高补体”小鼠品系中，有4个是最近从野生小鼠衍生而来的，其中一个品系SF/CamEi于1951年从野生小鼠衍生而来。其他三个品系BUB/BnJ、DA/HuSn和RIIIS/J是40多年前培育出来的，但此前显然未检测其补体活性。以BUB小鼠作为“高补体”小鼠的代表，我们检测了9种补体成分的水平，试图确定补体活性高的原因。在BUB和BDF1小鼠之间未检测到C1、C2、C4、C8或C9水平的差异。两个品系的C2活性都非常低。BUB小鼠的C3、C5、C6和C7活性高于BDF1小鼠，表明这些补体成分的差异是总补体活性差异的原因。决定“高补体”表型的基因在F1杂种中似乎是半显性的。“高补体”小鼠品系及其衍生的重组品系将在广泛的生物医学研究中发挥作用。
