A Single Autosomal Gene Controlling the Expression of the Extended Globoglycolipid Carrying SSEA-1 Determinant Is Responsible for the Expression of Two Extended Globogangliosides

Two extended globogangliosides, designated as Z1 and Z2, were purified from the kidney of DBA/2 mice. By means of GLC, 1H-NMR spectroscopy, negative-ion fast atom bombardment mass spectrometry, methylation analysis, and enzymatic digestion, the structures of Z1 and Z2 were determined to be NeuGcα2-3Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-Cer and NeuGcα2-8NeuGcα2-3Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-Cer, respectively. Since Z1 and Z2 were not detectable in the kidney of C57BL/10 and 6, BALB/c, and WHT/Ht mice, the mode of genetic control on Z1 and Z2 expression was examined by mating experiments between C57BL/10 or BALB/c and DBA/2. The results indicated that the expression of Z1 and Z2 is a recessive phenotype and that DBA/2 mice carry a single autosomal recessive gene. In the previous paper, we reported that DBA/2 mice do not express GL-Y (Galβ1-4(Fucα1-3)GlcNAcβ1-6(Galβ1-3)Gb4 Cer) but express GL-X (Galβ1-3Gb4Cer) in the kidney (J. Biochem. 101, 553–562 (1987)), and that a single autosomal defective gene responsible for the defective GL-Y expression was identified by genetic analysis (J. Biochem. 101, 563–568 (1987)). In the present study, the results of analysis of the expression of GL-Y, Z1, and Z2 in the kidney of backcross mice indicated that 42/83 mice did not express GL-Y but expressed GL-X, Z1, and Z2, and the other 41 mice expressed GL-Y but neither Z1 nor Z2. The absence of a single exception in 83 mice, i.e., mice having either one of the following two phenotypes, GL-Y(−), Z1(−), and Z2(−) or GL-Y(+), Z1(+), and Z2(+), indicates that either a single recessive gene controls the expression of GL-Y, Z1, and Z2, or possibly two genes linked at a distance of less than 1.2 (= 1/84) centimorgan are responsible. We propose a hypothesis to explain the mode of genetic control of the expression of these glycolipids.