INTRODUCTION

Transgenic mice are important adjuncts for the study of the pathophysiology and treatment of human hemoglobin disorders. Many inbred strains with spontaneous and induced mutations and engineered knockout and knockin lines are available (Table 12.1). Transgenic mice have both advantages and disadvantages for studying human disease. Most available mice are of mixed or poorly characterized genetic backgrounds and must be bred onto another inbred strain to obtain sustainable lines and consistent physiology. The choice of genetic background or the presence of a mixed background can affect both hematology and physiology.

Different inbred mouse strains, and male and female mice, can have different physiological characteristics, complicating the interpretation of some experiments. Mice have a higher plasma osmolarity than man and the 2,3-BPG content of mouse red cells is twice that of human erythrocytes. Inbred strains have five common α-globin chains and three common β-globin chains. The common C57BL/6 strain has only a single α- and β-globin chain; other strains can have two α- or two β-globin chains. When these are combined with human globin transgenes, many homotetramers due to the presence of interspecies αβ dimers result, some of which form tetramers with low oxygen affinity that will affect polymer formation and pathophysiology. These are some examples of factors likely to alter sickle cell mouse pathophysiology when compared with human.

THE TECHNOLOGY OF TRANSGENIC AND KNOCKOUT MICE

In the early 1980s cloned DNA was introduced into fertilized mouse embryos.