4.5 Article

Molecular cloning and characterization of NPC1L1 in the Chinese tree shrew (Tupaia belangeri chinensis)

Journal

MOLECULAR BIOLOGY REPORTS
Volume 48, Issue 12, Pages 7975-7984

Publisher

SPRINGER
DOI: 10.1007/s11033-021-06829-5

Keywords

Tree shrew; Cholesterol absorption; Entry of HCV

Funding

  1. Yunnan health training project of high-level talents [D-2018026]
  2. Yunnan science and technology talent and platform program [2018HB071, 2017HC019]
  3. Kunming Science and technology innovation team [2019-1-R-24483]
  4. National Natural Science Foundation of China [U1702282]

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The tree shrew NPC1L1 has a higher homology with human NPC1L1 compared to rodents. Its expression is highest in the small intestine, with detectable levels in the lung and pancreas. These findings are valuable for understanding the function of tsNPC1L1 in cholesterol absorption and HCV infection.
Background The Niemann-Pick C1-Like 1 protein, a multi-transmembrane domain molecule, is critical for intestinal cholesterol absorption, and is the entry factor for hepatitis C virus (HCV). The Chinese tree shrew (Tupaia belangeri chinensis) is closer to primates in terms of genetic evolution than rodents. Previous studies indicated that the tree shrew was suitable for HCV research; however, little is known about tree shrew NPC1L1. Methods and results TsNPC1L1 cDNA was amplified by rapid amplification of cDNA ends (RACE) technology. The cDNA sequence, its encoded protein structure, and expression profile were analyzed. Results indicated that the tsNPC1L1 mRNA is 4948 bp in length and encodes a 1326 amino acid protein. TsNPC1L1 possesses 84.97% identity in homology to human NPC1L1 which is higher than both mouse (80.37%) and rat (81.80%). The protein structure was also similar to human with 13 conserved transmembrane helices, and a sterol-sensing domain (SSD). Like human NPC1L1, the tsNPC1L1 mRNA transcript is highly expressed in small intestine, but it was also well-expressed in the lung and pancreas of the tree shrew. Conclusion The homology of tree shrew NPC1L1 was closer to human than that of rodent NPC1L1. The expression of tsNPC1L1 was the highest in small intestine, and was detectable in lung and pancreas. These results may be useful in the study of tsNPC1L1 function in cholesterol absorption and HCV infection.

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