# Novel Role of the ALPI Gene Associated with Constipation Caused by Complement Component 3 Deficiency

## TL;DR

This study identifies the ALPI gene as a novel contributor to constipation caused by a deficiency in complement component 3 (C3) in mice.

## Contribution

The study discovers ALPI as a novel gene associated with C3 deficiency-induced constipation through RNA profiling and functional validation.

## Key findings

- C3 knockout mice showed 1237 upregulated and 1292 downregulated genes compared to wild type.
- ALPI gene upregulation helped recover mucin-related gene expression and constipation phenotypes in C3 KO mice.
- ALPI is identified as a novel gene candidate linked to C3 deficiency-induced constipation.

## Abstract

Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D (KDM5D), olfactory receptor 870 (Olfr870), pancreatic lipase (PNLIP), and alkaline phosphatase intestinal (ALPI). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation.