title: Characterization of expression in mice of a transgene containing 3.3 kb of the human lactase-phlorizin hydrolase (LPH) 5' flanking sequence.
abstract: OBJECTIVE
  The regulation of human intestinal lactase-phlorizin hydrolase remains incompletely understood. One kb of pig and 2 kb of rat 5'-flanking sequence controls correct tissue, cell, topographic, and villus LCT expression. To gain insight into human LCT expression, transgenic mouse lines were generated from 3.3 kb of human LPH 5' flanking sequence from a lactase persistent individual fused to a human growth hormone (hGH) reporter bounded by an insulator.
  
  
  METHODS
  Four lines were identified in which reporter expression was specifically detectable in the intestine and no other organ, two of which demonstrated hGH expression specific to small and large intestine. Quantitative RT-PCR was carried out on proximal to distal segments of small intestine at fetal days 16.5 and 18.5 and at birth, postnatal days 7 and 28 in line 22.
  
  
  RESULTS
  In fetal intestine, hGH expression demonstrated a proximal to distal gradient similar to that in native intestine. There was no significant difference between hGH expression levels at 7 and 28 days in segment 3, the midpoint of the small intestine, where expression of endogenous lactase is maximal at 7 days and declines significantly by 28 days. Distal small intestine displayed high levels of hGH expression in enteroendocrine cells, which were shown to be a subset of the PYY cells.
  
  
  CONCLUSIONS
  Thus, a 3.3-kb LPH 5' flanking sequence construct from a lactase persistent individual is able to maintain postnatal expression in transgenic mice post weaning.
authors.affiliation: Gastrointestinal Cell, Molecular Biology Laboratory, Division of Gastroenterology and Nutrition, Children's Hospital Boston, and Department of Pediatrics, Harvard Medical School, Enders 609.2, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Nana Yaa
authors.initials: NY
authors.lastname: Baffour-Awuah
authors.forename: Eveline
authors.initials: E
authors.lastname: Delemarre
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Jarom
authors.initials: J
authors.lastname: Heijmans
authors.forename: David
authors.initials: D
authors.lastname: Boerwinkel
authors.forename: Selma
authors.initials: S
authors.lastname: Algra
authors.forename: John J
authors.initials: JJ
authors.lastname: Fialkovich
authors.forename: Shabana
authors.initials: S
authors.lastname: Islam
authors.forename: Tjalling
authors.initials: T
authors.lastname: Bosse
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Grand
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Krasinski
authors.forename: Robert K
authors.initials: RK
authors.lastname: Montgomery
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology; D005260:Female; D005333:Fetus / Q000201:enzymology; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D010694:Lactase-Phlorizin Hydrolase / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D013006:Growth Hormone; D010694:Lactase-Phlorizin Hydrolase