title: Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4.
abstract: Glucosaminyl N-deacetylase/N-sulfotransferases (NDSTs) are the first enzymes that mediate the initiation of heparan sulfate sulfation. We previously identified NDST4 as a putative tumor suppressor in human colorectal cancer. In the study, we generated an Ndst4 knockout (Ndst4-/-) mouse strain and explored its phenotypic characteristics, particularly in the development of colonic epithelial homeostasis. The Ndst4-deficient mice were viable and fertile, and their life spans were similar to those of wild-type littermates. No gross behavioral or morphological differences were observed between the Ndst4-/- and wild-type mice, and no significant changes were determined in the hematological or serum biochemical parameters of the Ndst4-/- mice. Ndst4 RNA transcripts were expressed in the brain, lung, gastrointestinal tract, pancreas, and ovary. However, Ndst4-null mice exhibited no gross or histological abnormalities in the studied organs, except for the colon. Although no alterations were observed in the crypt length or number of proliferating cells, the Ndst4-/- mice exhibited an increased number of goblet cells and a decreased number of colonocytes in the proximal colon compared with the wild-type mice. Moreover, Ndst4 deficiency increased the basal level of apoptosis in the colonic epithelium. Taken together, we established, for the first time, an Ndst4-/- mouse strain and revealed the involvement of Ndst4 in the development and homeostasis of colonic epithelium. Accordingly, NDST4 in human colon might direct the biosynthesis of specific heparan sulfate proteoglycans that are essential for the maintenance of colonic epithelial homeostasis. Thus, the loss of its function may result in the tumorigenesis and progression of colorectal cancer.
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Tzu-Ming
authors: TM
authors: Jao
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Ya-Lin
authors: YL
authors: Li
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Shu-Wha
authors: SW
authors: Lin
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Sheng-Tai
authors: ST
authors: Tzeng
authors: Laboratory Animal Center, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: I-Shing
authors: IS
authors: Yu
authors: Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan.
authors: Sou-Jhy
authors: SJ
authors: Yen
authors: Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan.|School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors: Ming-Hong
authors: MH
authors: Tsai
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Ya-Chien
authors: YC
authors: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis; D002478:Cells, Cultured; D003106:Colon / Q000473:pathology* / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology*; D020397:Goblet Cells / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D019812:Heparan Sulfate Proteoglycans; C486032:Ndst4 protein, mouse; D015238:Sulfotransferases
keywords: NDST4; Ndst4 knockout mouse; heparan sulfate proteoglycan; tumor suppressor gene