Murine Model for Selective Transection of Intestinal Autonomic Nerves

Chenglin Xin; Bihan Liu; Zhijun Zhao; Yuankang Yang; Zhi Zheng; Zimeng Wang; Jun Zhang; Dan Tian; Jie Yin; Zhongtao Zhang

doi:10.3791/70861

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Method Article

Murine Model for Selective Transection of Intestinal Autonomic Nerves

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DOI:

10.3791/70861

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June 30th, 2026

Chenglin Xin^*¹^,²^,³^,⁴ , Bihan Liu^*¹^,²^,³^,⁴ , Zhijun Zhao^*¹^,²^,³^,⁴ , Yuankang Yang¹^,²^,³^,⁴ , Zhi Zheng¹^,²^,³^,⁴ , Zimeng Wang¹^,²^,³^,⁴ , Jun Zhang¹^,²^,³^,⁴ , Dan Tian¹^,²^,³^,⁴ , Jie Yin¹^,²^,³^,⁴ , Zhongtao Zhang¹^,²^,³^,⁴

¹Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, ²National Clinical Research Center for Digestive Diseases, ³State Key Lab of Digestive Health, ⁴Beijing Key Laboratory of Cancer Invasion and Metastasis Research

^* These authors contributed equally

Summary

This protocol aims to enable precise, selective transection of intestine-innervating sympathetic and parasympathetic nerves in mice using the superior mesenteric artery as a consistent anatomical landmark, providing a focused and reproducible model to study autonomic regulation of intestinal physiology and disease.

Abstract

Autonomic nerves comprise the sympathetic and parasympathetic systems, which act in a largely antagonistic manner to regulate diverse physiological functions. With growing interest in the roles of autonomic innervation in intestinal physiology and pathology, there is an increasing need for experimental models that enable precise manipulation of gut-directed sympathetic and parasympathetic inputs. Here, we present a surgical protocol to selectively transect the sympathetic and parasympathetic nerves innervating the intestine. Using the superior mesenteric artery (SMA) as a reproducible anatomical landmark, this approach allows reliable identification of intestinal autonomic nerve bundles and subsequent targeted transection. In contrast to broader denervation approaches such as ganglionectomy or subdiaphragmatic vagotomy, this approach is intended to achieve a more anatomically localized transection of intestine-directed autonomic bundles, which may help reduce extra-intestinal interference. The injury is controllable and is typically associated with minimal bleeding, supporting procedural consistency and postoperative recovery. Although the surgery requires appropriate microsurgical training, the protocol is adaptable, enabling users to tailor key parameters to specific experimental aims. Importantly, this model provides a practical platform to investigate the roles of sympathetic and parasympathetic nerves in regulating intestinal function under both physiological and disease conditions. This article aims to describe the procedure in detail to facilitate its adoption by new users in their research.

Introduction

The gastrointestinal tract is under continuous control of the autonomic nervous system (ANS), with sympathetic and parasympathetic pathways coordinating fundamental aspects of intestinal physiology, including motility, secretion, epithelial barrier function, and immune homeostasis¹^,². In the colon, extrinsic sympathetic inputs can exert region-dependent effects across multiple cellular compartments, underscoring that broad ANS perturbations may obscure site-specific intestinal phenotypes¹. Conversely, parasympathetic circuits, classically mediated by vagal signaling and downstream choli....