Inheritance of a heme-binding protein in rabbits.

LECTROPHORETIC variants of serum proteins which bind hemoglobin E have been referred to in man (SMITHIES and WALKER 1956) and swine (KRISTJANSSON 1961) as haptoglobins. IMLAH (1964) found that these same electrophoretic variants of swine could be demonstrated only if old homoglobin or alkaline hematin rather than fresh hemoglobin was added to swine sera prior to electrophoresis. Consequently IMLAH ( 1964) renamed this polymorphic protein “haem-binding globulin.” The polymorphic serum protein of rabbits which is to be described, exhibits somewhat similar characteristics to the “haem-binding globulin” of swine and will be tentatively designated “heme-binding protein” (Hbp) for reasons which will be discussed later (see DISCUSSION). In a pioneer study using starch gel electrophoresis, SMITHIES (1 955) demonstrated three distinct patterns of haptoglobins in human sera. These patterns were found by SMITHIES and WALKER (1956) to be controlled by two autosomal alleles Hp‘ and Hpz. Later, SMITHIES, CONNELL and DIXON (1962) and CONNELL, DIXON and SMITHIES (1962) subjected purified haptoglobin to reductive cleavage and electrophoresis in a starch gel containing mercaptoethanol and 8111 urea at acid pH, and were able to show that haptoglobin consisted of an alpha and beta chain. Three alpha chains were found to be controlled by three alleles-Hp’”’, Hp”, and Hp2-which could form six possible genotypes, all distinguishable by the above procedure. Using this same procedure, NANCE and SMITHIES (1963) found unusual phenotypes in a Brazilian population which were explained by hypothesizing the alleles HPFF7 Hpzss, and Hp2(FS) in place of H P . SHIM, LEE, and KANG (1965) have presented evidence for three alleles, named HpP”, Hpfi‘, and HpfiL, which control the inheritance of beta chains of human haptoglobins. GIBLETT (1964) has referred to 11 variant haptoglobin phenotypes of man in addition to the three types first described. Electrophoretic variants of haptoglobins have not been described in many other species. KRISTJANSSON (1961 ) described six phenotypes of haptoglobins in swine sera. The synthesis of these haptoglobins was shown to be under the control of three codominant alleles. A fourth allele and its corresponding haptoglobin was discovered by HESSELHOLT (1963). This system of haptoglobins was later referred to as a system of “haem-binding globulins” (IMLAH 1964) as mentioned