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Perpetua: The Journal of Undergraduate Research at UAH

College

College of Science

Department

Biological Sciences

Abstract

Tyrosinemia type I (TT1) is a rare meta-bolic disorder that results in mutations of the enzyme FAH, which is responsible for tyrosine breakdown. Without the current treatment of 2-(2-nitro-4-trifluo-romethylbenzoyl) cyclohexane-1-3-dione (NTBC), toxic metabolites build up causing severe kidney and liver dysfunction that can lead to mortality. Cognitive and social defects have recently been observed in af-fected individuals on NTBC, and to investigate these effects mice with tyrosinemia type I were tested uti-lizing the Crawley three-chambered sociability test. Social behavior is analyzed in the three chambered apparatus by observing mice interaction with either a real or dummy mouse, or between a familiar or novel mouse. The results show that mice with tyrosinemia type I spend twice as much time investigating a dummy mouse compared to a real mouse, indicating sociability deficits. Due to the importance of olfac-tion in mouse behavior, the olfactory abilities of the mice were also analyzed by means of the buried food test. In order to assess a biological basis for these so-cial and cognitive impairments, mice brains were stained using Luxol fast blue to visualize myelin in the cerebral cortex. Microscopic analysis of the stained cerebral cortex showed hypermyelination in mice with tyrosinemia type I in comparison to con-trols. The cognitive and sociability issues observed in tyrosinemia type I mice could be attributed to mal-formed neuronal pathways and synapses caused by hypermyelination of the cerebral cortex.

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