Haploinsufficiency of the Tyrosine Hydroxylase Gene in the Inbred C57BL/6J Strain Alters Behavior, Immunity, and Oxidative Stress, Especially After Acute Stress

Abstract

Catecholamines (CA) are considered to play key roles in acute stress responses, but they also regulate important functions of the nervous, immune, and endocrine systems and are essential for body homeostasis and health. In Swiss mice (an outbred strain) with haploinsufficiency of the tyrosine hydroxylase gene (Th, TH-HZ), which encodes the rate-limiting enzyme of catecholamine synthesis, impairments in homeostatic system functions and a reduced lifespan have been reported. Moreover, these homeostatic alterations are exacerbated when these animals are exposed to acute restraint stress. Nonetheless, the effects of this genetic modification on an inbred strain, such as C57BL/6J, are undetermined. Given that the genetic background of mice can affect the phenotype of any genetic modification, this work aimed to characterize how behavioral responses, immunity, and the oxidative state in C57BL/6J mice are altered by Th haploinsufficiency under basal conditions after being subjected to 10 min of acute restraint stress. Sex differences were also considered. Compared with their WT counterparts, TH-HZ C57BL/6J animals exhibit behavioral impairments, immunosenescence, and oxidative stress under basal conditions. After stress, TH-HZ animals (both sexes) exhibit deteriorated behavior and immune functions. Therefore, Th haploinsufficiency in the inbred C57BL/6J strain triggers impairments in behavior, immunity, and the redox state. These findings corroborate the role of CA in maintaining regulatory system functions and highlight the importance of mouse strains in basic research.