Ndst4-KO Mouse

Ndst4, a member of the glucosaminyl N-deacetylase/N-sulfotransferase (NDST) family, is involved in heparan sulfate sulfation initiation [4]. It maps to human chromosome 4q26 and may be associated with the serotonergic synapse signaling pathway, as well as having potential links to resistin level regulation [3,5].

An Ndst4 knockout (Ndst4-/-) mouse strain was generated. Ndst4-/-mice showed no gross or histological abnormalities in most organs except the colon, where there was an increased number of goblet cells, a decreased number of colonocytes in the proximal colon, and an increased basal level of apoptosis in the colonic epithelium. This indicates Ndst4's involvement in the development and homeostasis of the colonic epithelium [2]. In colorectal cancer, NDST4 is a novel candidate tumor suppressor gene. Its genetic loss was significantly associated with advanced pathological stage and poorer overall survival of patients, suggesting its role in CRC progression [1].

In conclusion, Ndst4 plays a crucial role in maintaining colonic epithelial homeostasis, likely through directing the biosynthesis of specific heparan sulfate proteoglycans. Its loss of function may contribute to the tumorigenesis and progression of colorectal cancer, as demonstrated by the Ndst4 knockout mouse model [1,2].