Slc35b3-KO Mouse

Slc35b3, known as solute carrier family 35 member B3, is a transferase involved in the synthesis of 3'-phosphoadenosine-5'-phosphosulfate (PAPS), which plays a key role in mucin sulfation [1]. It is part of the aryl hydrocarbon receptor (AHR)-Papss2-Slc35b3 pathway, contributing to the maintenance of intestinal epithelial homeostasis [1].

In a study on inflammatory bowel disease (IBD), a high-fat diet (HFD) led to a decrease in indole-3-acetic acid (IAA) and intestinal barrier damage. IAA supplementation enhanced intestinal mucin sulfation and alleviated colitis by upregulating Papss2 and Slc35b3 via the AHR [1]. Oral administration of Lactobacillus reuteri, which produces IAA, protected against colitis and promoted mucin sulfation, while a modified strain lacking the ability to produce IAA did not [1]. In addition, in non-small cell lung cancer (NSCLC), there were nominally significant associations between copy number variations (CNVs) and the SLC35B3 gene [2]. Also, in muscle-invasive bladder cancer, a 9-gene signature including SLC35B3 could predict response to neoadjuvant chemotherapy [3].

In conclusion, Slc35b3 is crucial for maintaining intestinal epithelial homeostasis through its role in mucin sulfation. Its upregulation by IAA via the AHR pathway has implications for IBD treatment. Additionally, the associations of SLC35B3 with CNVs in NSCLC and its role in predicting chemotherapy response in muscle-invasive bladder cancer suggest its significance in cancer-related research.

References:

1. Li, Mengfan, Ding, Yiyun, Wei, Jingge, Su, Xiaomin, Cao, Hailong. 2024. Gut microbiota metabolite indole-3-acetic acid maintains intestinal epithelial homeostasis through mucin sulfation. In Gut microbes, 16, 2377576. doi:10.1080/19490976.2024.2377576. https://pubmed.ncbi.nlm.nih.gov/39068517/

2. Heo, Yeonjeong, Heo, Jeongwon, Han, Seon-Sook, Cheong, Hyun Sub, Hong, Yoonki. 2020. Difference of copy number variation in blood of patients with lung cancer. In The International journal of biological markers, 36, 3-9. doi:10.1177/1724600820980739. https://pubmed.ncbi.nlm.nih.gov/33307925/

3. Hepburn, Anastasia C, Lazzarini, Nicola, Veeratterapillay, Rajan, Bacardit, Jaume, Heer, Rakesh. 2021. Identification of CNGB1 as a Predictor of Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer. In Cancers, 13, . doi:10.3390/cancers13153903. https://pubmed.ncbi.nlm.nih.gov/34359804/