AbstractIn this study we compared the α‐calcitonin gene‐related peptide (αCGRP) and βCGRP expression patterns in wild‐type and knockout mice by using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. In dorsal root ganglia and spinal cord of wild‐type animals, αCGRP mRNA was about two times more abundant than βCGRP mRNA. The βCGRP mRNA was the only isoform expressed in the intestine. In αCGRP knockout mice, we found no change in βCGRP mRNA levels in dorsal root ganglia and spinal cord compared with wild‐type controls, but a twofold decrease in the intestine. CGRP immunoreactivity (IR) was detected in many small and some large neurons in the dorsal root ganglia, was found in sensory fibers and motor neurons in the spinal cord, and labeled neuromuscular junctions in wild‐type mice. In the dorsal root ganglia of αCGRP knockout mice, punctate βCGRP‐IR again was predominantly found in small neurons. In the spinal cord, βCGRP‐IR fibers were localized to the outermost layer of the dorsal horn. IR was found in the cell bodies of motor neurons, but it was undetectable in neuromuscular junctions. In the intestine, CGRP‐IR was localized to neurons of the myenteric plexus and to fibers in the mucosal folds, with similar staining intensity in both wild‐type and knockout mice. Finally, CGRP‐IR was undetectable in preganglionic fibers and postganglionic sympathetic neurons in mice from both genotypes. Our results indicate that αCGRP and βCGRP are variably coexpressed in different functional aspects of the mouse nervous system. This pattern suggests distinct roles for βCGRP in pain, neuromuscular, and gastrointestinal systems. J. Comp. Neurol. 476:32–43, 2004. © 2004 Wiley‐Liss, Inc.