Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone β1 receptor gene

Michael P. McDonald, Rosemary Wong, Gregory Goldstein, Bruce Weintraub, Sheue Yann Cheng, Jacqueline Crawley

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor β (TRβ) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TRβ gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRβ gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRβ gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD.

Original languageEnglish (US)
Pages (from-to)289-301
Number of pages13
JournalLearning and Memory
Issue number4-5
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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