Transgenic mice expressing a human mutant β1 thyroid receptor are hyperactive, impulsive, and inattentive

WB Siesser, J Zhao, LR Miller… - Genes, Brain and …, 2006 - Wiley Online Library
WB Siesser, J Zhao, LR Miller, SY Cheng, MP McDonald
Genes, Brain and Behavior, 2006Wiley Online Library
Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed childhood
psychiatric disorder. We have found that a transgenic mouse bearing a human mutant
thyroid receptor (TRβ1) expresses all of the defining symptoms of ADHD—inattention,
hyperactivity, and impulsivity—as well as a 'paradoxical'response to methylphenidate
(MPH). As with ADHD, the behavioral phenotypes expressed by the TRβ transgenic mice
are dynamic and sensitive to changes in environmental conditions, stress, and …
Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed childhood psychiatric disorder. We have found that a transgenic mouse bearing a human mutant thyroid receptor (TRβ1) expresses all of the defining symptoms of ADHD—inattention, hyperactivity, and impulsivity—as well as a ‘paradoxical’ response to methylphenidate (MPH). As with ADHD, the behavioral phenotypes expressed by the TRβ transgenic mice are dynamic and sensitive to changes in environmental conditions, stress, and reinforcement. TRβ transgenic mice are euthyroid except for a brief period during postnatal development, but the behavioral phenotypes, elevated dopamine turnover, and paradoxical response to MPH persist into adulthood. Thus, like the vast majority of children with ADHD, the TRβ transgenic mice exhibit the symptoms of ADHD in the complete absence of thyroid abnormalities. This suggests that even transient perturbations in developmental thyroid homeostasis can have long‐lasting behavioral and cognitive consequences, including producing the full spectrum of symptoms of ADHD.
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