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In mammals, including most human populations, intestinal lactase activity is very high in the suckling and declines to low levels after weaning. There are two lactase phenotypes among human adults, one with persistent high lactase activity and one with hypolactasia(1). In the present study lactase mRNA levels have been measured by cDNA probes on northern blot of poly(A)+RNA normalized by B-actin in the small intestine of raboit, at different ages, and on slot blots of total RNA and polyiA)+RNA of human adults with persistent high lactase activity and with hypolactasia. An ECO RI-Hind III fragment covering more than the 5'-half of the rabbit lactase cDNA and the full human lactase cDNA were used as probes (2). mRNA levels have been compared with those of lactase activity (3). In the rabbit mRNA appears by the end of the gestational period and a level, comparable to that found in the suckling animal, is still present in the adult life. The lactase activity appears at the same time of the mRNA, but it declines to very low levels postweaning. Similarly, in man, at RNA level, no clear differences were found between adults with hypolactasia and adults with persistent high lactase activity.Conclusion: In adult mammals and in adult human hypolactasia, the control of lactase gene expression is very likely to be at a post-transcriptional level. 1) Auricchio S. et al. Lancet 2,324-326, 1963; 2) Mantei N. et al. The EMBO J.7, 2705-2713, 1988; 3) Asp NG. et al. Anal. Biochem. 47,527-538,1972.

The adult-type hypolactasia is a condition due to homozigosity for a recessive allele of a hypothetic regulatory gene which controls the lactase activity in the adulthood. It is still unclear whether this regulatory gene is part of the lactase gene itself or maps to a different locus. To investigate this aspect, we have used a genetic approach: the analysis of family segregation of both the lactase gene and the lactose absorption capacity, which correlates with the lactase activity. 8 Italian families (20 meioses) entered this study. Families were chosen on the basis of the coexistence of subjects with either hypolactasia or persistence of high lactase activity. The lactose absorption capacity was assessed by breath-test after an oral load of 50 g of lactose. To follow the lactase gene segregation, we searched for RFLPs identified by the lactase cDNA. DNA of each subject was digested by the following restriction enzymes, which we found to detect RFLPs of the lactase gene: Pst I, Msp I, Rsa I, Bel I. in all the informative pedigrees, cosegregation of the lactase gene and the hypolactasic condition has been observed. This result suggests that an event involving the lactase gene itself (e.g. regulation by sequences at the promoter; different RNA editing or splicing) can lead to either hypolactasia or, by mutation, to the persistence of high lactase activity. Indeed, we cannot exclude that hypolactasia might be a heterogeneous condition, in which also other mechanisms (e.g. post-translational modification) may control in trans- the lactase gene expression.