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Background/aims: We have previously shown that in the proximal-jejunum of hypolactasic humans, just a few villus enterocytes express lactase protein and activity. In the present study, we compared the distribution of lactase messenger RNA (mRNA), protein, and activity in villus enterocytes in tissues obtained from subjects with persistent high lactase activity and those with hypolactasia., Methods: Immunohistochemical and enzymohistochemical staining was performed on closely adjacent sections of human proximal jejunum from 5 individuals with persistent high lactase activity and 32 with hypolactasia. In all the persistent and in 9 hypolactasic samples, in situ hybridization was also performed using a digoxygenin-labeled RNA probe., Results: In persistent tissues, lactase mRNA, protein, and activity were present in all villus enterocytes. In hypolactasic tissues, lactase mRNA was detected only in some villus enterocytes; some of them also expressed protein and activity, whereas others did not. In 8 of these hypolactasic samples, a variable number of villus enterocytes with lactase mRNA and protein did not express lactase activity., Conclusions: Various types of enterocytes are present even on a single villus from individuals with adult-type hypolactasia. These results show that different mechanisms control lactase expression in enterocytes on the same villus.

Background: The authors have shown that a mosaicism of brush border antigens may occur spontaneously on enterocytes of small intestine in human adult-type hypolactasia. The present paper gives another example of spontaneously occurring mosaicism as indicated by the patchy expression of blood group antigens on villus enterocytes., Methods: Thirty-five individuals were examined by immunomorphological techniques with antibodies against blood group antigens., Results: In 4 of 16 A blood group individuals, the blood group antigens were expressed only in some villus enterocytes. The individuals with this mosaic pattern were all shown to be nonsecretors. The A antigen in the positive enterocytes of these individuals was only present as the ALe(b) structure, whereas ALe(y) and ALe(d) were also present in the secretors. The patches of positive enterocytes were randomly distributed along the villus wall., Conclusions: A nonsecretor individuals express the blood group antigens only in some villus enterocytes; this mosaicism does not arise from a heterogeneous population of stem cells within the crypts but rather reflects subtle differences in the pattern of differentiation between monoclonally derived epithelial cells on the villus.

Enzymatic and immunohistological analyses of lactase were performed at different stages of development and within different regions of the small intestine of the rabbit and rat. As previously reported, there seems to be a sharp decline of lactase activity on weaning but variable and higher levels of activity are seen in adult animals. Two monoclonal antibodies to rat lactase were available to study the protein in rats. Four monoclonal antibodies to human lactase were shown to cross-react with rabbit lactase and used for the rabbit studies. Immunohistological analysis of small intestine of adult rabbits and rats showed residual lactase protein within the enterocytes throughout the small intestine. In the middle of the small intestine (lower jejunum, upper ileum), uniform staining of the brush border was observed. In the proximal and distal regions, a patchy pattern of staining was observed. This pattern, which resembles that observed in adult hypolactasic humans, indicates an underlying heterogeneity of enterocyte differentiation.

Immunohistological analysis of the expression of lactase protein in adults with hypolactasia has been carried out using monoclonal antibodies. Eight different antibodies that recognize at least three distinct epitopes on the lactase protein each gave the same result. Strong brush border staining was observed in all the lactase-persistent adults. No staining at all was detected in 9 of the hypolactasic subjects. In the remaining 12 individuals a mosaic pattern of expression was observed: small patches of enterocytes stained strongly, whereas the surrounding areas showed no staining at all. Sucrase-isomaltase, in contrast, showed no such mosaicism in these or in any of the other individuals. The mosaicism observed in the 12 hypolactasic individuals suggests that the differentiation of the columnar cells along the villus is not homogeneous. Furthermore, the existence of two patterns of expression of the lactase protein in the lactase-deficient individuals (i.e., absence of protein and mosaicism), if characteristic of the entire length of the intestine of the individuals tested, would suggest the existence of two phenotypes of adult-type hypolactasia in the population studied.