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Review
. 2025 May 30;26(11):5262.
doi: 10.3390/ijms26115262.

Experimental Animal Models of Phenylketonuria: Pros and Cons

N A Bobrova  1 , D I Lyubimova  2 , D M Mishina  2 , V S Lobanova  3 , S I Valieva  3 , O N Mityaeva  1   4 , S G Feoktistova  1 , P Yu Volchkov  1   4   5
Affiliations
Review

Experimental Animal Models of Phenylketonuria: Pros and Cons

N A Bobrova et al. Int J Mol Sci. .

Abstract

Phenylketonuria (PKU) is a common inherited metabolic disorder characterised by impaired metabolism of the amino acid phenylalanine. The disease results from a mutation in the phenylalanine hydroxylase (PAH) enzyme, which converts phenylalanine (Phe) into tyrosine (Tyr). The absence or inactivity of this enzyme results in significantly elevated levels of Phe in the blood, which can lead to severe neurological conditions, including intellectual disability, epilepsy, and other developmental disorders. Since its discovery, animal models have played a crucial role for understanding the pathophysiology of PKU, as well as providing recognisable proof of targets and surveying new remedial specialists and in vivo medicines. In the present study, we conducted a comprehensive review of the experimental and non-experimental animal models employed for phenylketonuria and its associated complications.

Keywords: animal models; metabolic disorder; phenylalanine; phenylalanine hydroxylase; phenylketonuria.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Metabolic pathway of PKU: Phenylalanine hydroxylase (PAH) catalyses the hydroxylation of L-phenylalanine to L-tyrosine. In the case of phenylketonuria, the reaction fails, and phenylalanine levels increase (the arrow up) and tyrosine levels fall (the arrow down).
Figure 2
Figure 2
Pig models for the study of phenylketonuria.
Figure 3
Figure 3
Zebrafish models for the study of phenylketonuria.
Figure 4
Figure 4
Avian models for the study of phenylketonuria.
See this image and copyright information in PMC

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