Sporadic midbrain dopamine neuron abnormalities in laboratory mice

We report an anatomical abnormality of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) in different strains of inbred and outbred mice, one mouse strain (C57BL/6, B6) from different commercial suppliers, and in B6J mice bred internally. The abnormality consisted of a sporadic and unpredictable decrease in the number of dopaminergic neurons and/or a reduction or complete loss of tyrosine hydroxylase (TH) staining in a focal subset of neurons of the SNpc and/or VTA. This abnormality had a preference for a unilateral right side location, but could affect one or both sides of each subregion independently or together. The frequency and severity were variable between and within strains and colonies. The neuronal abnormality was found in mice from the five commercial suppliers examined, 5/15 inbred strains from a single supplier, and the one outbred strain (CD1) examined. The striatal content of catecholamines was not affected by this abnormality even when there was significant asymmetric TH neuronal loss, but did vary significantly between commercial suppliers. Manipulations in housing conditions did not affect the abnormalities. The mechanism and cause of this abnormality could not be determined in this study although several potential factors were eliminated. The frequent, but not universal, occurrence of this abnormality has significant implications for the use of laboratory mice in studying the midbrain dopamine system and warrants its recognition, knowledge of their frequency, and exploration of a mechanism to address or eliminate them.