WBR0369

Author	[[PageAuthor::Serge Korjian, M.D., Gonzalo A. Romero, M.D. [1](Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry, MainCategory::Pathology, MainCategory::Pathophysiology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A research lab develops a new knock-in mouse model with a chimeric mouse/human exon containing 140 CAG repeats inserted into a gene located on the short arm of chromosome 4. The mice are grown and observed for 18 months. All mice develop increased locomotor activity and abnormal posturing around 1 month of age, followed by hypoactivity at 4 months and gait abnormalities at 1 year. Which of the following neurochemical changes is associated with this syndrome?]]
Answer A	AnswerA::Decreased norepinephrine, Decreased serotonin, Decreased dopamine
Answer A Explanation	[[AnswerAExp::These are the neurotransmitter changes associated in depression]]
Answer B	AnswerB::Increased norepinephrine, Increased serotonin, Increased dopamine
Answer B Explanation	[[AnswerBExp::This is seen in schizophrenia]]
Answer C	AnswerC::Increased acetylcholine, Increased serotonin, Decreased dopamine
Answer C Explanation	[[AnswerCExp::These changes are seen in parkinson’s disease]]
Answer D	AnswerD::Decreased GABA, Decreased acetylcholine, Increased dopamine
Answer D Explanation	AnswerDExp::These changes are associated with Huntington disease.
Answer E	AnswerE::Increased norepinephrine, Decreased GABA, Decreased serotonin
Answer E Explanation	[[AnswerEExp::These neurotransmitter changes are seen in anxiety]]
Right Answer	RightAnswer::D
Explanation	[[Explanation::The mouse model presented is an experimental approach for the investigation of Huntington's disease. The disorder has an autosomal dominant inheritance with the huntingtin gene on chromosome 4p harboring an expansion of the CAG repeats Educational Objective: Huntington's disease is an autosomal dominant disorder caused by a CAG trinucleotide expansion in the huntingtin gene on chromosome 4p. It is characterized by caudate atrophy leading to a decrease in GABA and acetylcholine, and an increase in dopamine. References: First Aid 2013 page 461 Menalled LB, Sison JD, Dragatsis I, Zeitlin S, Chesselet MF. Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats. J Comp Neurol. 2003;465(1):11-26. Crow TJ, Baker HF, Cross AJ, et al. Monoamine mechanisms in chronic schizophrenia: post-mortem neurochemical findings. Br J Psychiatry. 1979;134:249-56.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Huntington's disease, WBRKeyword::GABA, WBRKeyword::Serotonin, WBRKeyword::CAG, WBRKeyword::Trinucleotide repeat disorders, WBRKeyword::caudate
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