DEVELOPMENTAL EXPRESSION OF SI IS REGULATED IN TRANSGENIC MICE BY AN EVOLUTIONARILY CONSERVED PROMOTER

Developmental expression of the sucrase-isomaltase (SI) gene in the mo use intestine involves two major transitions that correspond to critic al developmental events. Low levels of SI mRNA were first identified i n day 16.5 fetal mouse intestine, immediately after the transition fro m stratified endoderm to a columnar epithelium organized in nascent vi lli. Low levels were maintained until the third week of life, when ind uction of SI mRNA to adult levels was observed coincident with the tim e of weaning. The mechanism of this pattern of SI gene expression was studied in transgenic mice using a reporter gene construct containing an SI gene promoter that is evolutionarily conserved between mouse and human (nucleotides -201 to +54 of the mouse SI gene). This promoter i ncluded the necessary regulatory information to direct transcription t o enterocytes in developmental and differentiation-dependent patterns that recapitulated the expression of the endogenous SI gene. However, transgenes lacked the ability to direct induction of precocious expres sion in suckling animals after administration of corticosteroids. Thes e findings define a short SI gene promoter that contains cis-acting el ements that are responsible for developmental and differentiation-depe ndent transcriptional regulation.