Lab Anim Res.  2018 Dec;34(4):257-263. 10.5625/lar.2018.34.4.257.

Disruption of the Tff1 gene in mice using CRISPR/Cas9 promotes body weight reduction and gastric tumorigenesis

• Kim H
• Jeong H
• Cho Y
• Lee J
• Nam KT
• Lee HW

• KMID: 2459303
• DOI: http://doi.org/10.5625/lar.2018.34.4.257

Abstract

Trefoil factor 1 (TFF1, also known as pS2) is strongly expressed in the gastrointestinal mucosa and plays a critical role in the differentiation of gastric glands. Since approximately 50% of all human gastric cancers are associated with decreased TFF1 expression, it is considered a tumor suppressor gene. TFF1 deficiency in mice results in histological changes in the antral and pyloric gastric mucosa, with severe hyperplasia and dysplasia of epithelial cells, resulting in the development of antropyloric adenoma. Here, we generated TFF1-knockout (KO) mice, without a neomycin resistant (NeoR) cassette, using the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRSIPR/Cas9) system. Though our TFF1-KO mice showed phenotypes very similar to the previous embryonic stem (ES)-cell-based KO mice, they differed from the previous reports in that a reduction in body weight was observed in males. These results demonstrate that these newly established TFF1-KO mice are useful tools for investigating genetic and environmental factors influencing gastric cancer, without the effects of artificial gene insertion. Furthermore, these findings suggest a novel hypothesis that TFF1 expression influences gender differences.

Keyword

Tff1; gastric cancer; CRISPR/Cas9; Tff1-knockout mouse

MeSH Terms

Adenoma
Animals
Body Weight*
Carcinogenesis*
Epithelial Cells
Gastric Mucosa
Genes, Synthetic
Genes, Tumor Suppressor
Humans
Hyperplasia
Lotus
Male
Mice*
Mucous Membrane
Neomycin
Phenotype
Stomach Neoplasms
Neomycin