Efferent signals from the vagus nerve are thought to mediate both basal and meal-induced gastric acid secretion and to provide trophic support of the gastric mucosa. However, the underlying mechanisms are still poorly understood. Neurturin, signaling via GDNF-family receptor a2 (GFRa2), is essential for the parasympathetic innervation of many target tissues but its role in gastric innervation is unknown. Here we found that most, including all GRP-positive nerve fibers in wild-type mouse gastric mucosa were cholinergic. GFRa2-KO mice lacked virtually all cholinergic nerve fibers and associated glial cells in the gastric mucosa but not in the smooth muscle, consistent with the selective expression of neurturin mRNA in the gastric mucosa. Importantly, vagal stimulation by 2-deoxyglucose and chemical vagotomy by hexamethonium failed to affect acid secretion in GFRa2-KO mice consistent with their lack of functional innervation in gastric mucosa. Surprisingly, basal and maximal histamine-induced acid secretion did not differ between wild-type and GFRa2-KO mice. Moreover, circulating gastrin levels in both fasted and fed animals, thickness of gastric mucosa, and density of parietal and endocrine cells were similar between the genotypes. Interestingly, atropine seemed to reduce basal acid output in GFRa2-KO mice similarly as in wild-type mice, suggesting constitutively active muscarinic receptors. Our results show that the efferent innervation of gastric mucosa depends on neurturin-GFRa2 signaling but is dispensable for normal gastrin secretion and for basal and maximal gastric acid output. Thus, basal acid and secretion seems autonomous but can be modulated by neurocrine signals. GFRa2-KO mice provide a useful model to study neural regulation of gastric mucosal functions.