. Author manuscript; available in PMC: 2021 Nov 20.

Published in final edited form as: Nat Rev Dis Primers. 2021 May 20;7(1):36. doi: 10.1038/s41572-021-00267-0

Table 1 |.

Animal models of PKU

Animal	Method of generating model	Genetic background	Comparison with patients with PKU		Ref.
Animal	Method of generating model	Genetic background	Biochemical	Clinical	Ref.
Rat	Give large amounts of phenylalanine in combination with para-chloro-Phe, α-methyl-Phe or both	Various, usually Wistar	Resembles BH4 defects rather than PKU	Resembles BH4 defects rather than PKU	²⁴⁰
Mouse	Enu-1 (ENU-induced random mutagenesis)	BTBR	Mild HPA with Phe challenge	Models BH4-responsive PAH deficiency	⁴⁶
	Enu-2 (ENU-induced random mutagenesis)	BTBR	High blood and brain Phe concentrations in line with PKU	Behavioural and memory issues, partly also perhaps in relation with BTBR-specific features, such as lack of corpus callosum	⁴⁹
	Enu-2 (ENU-induced random mutagenesis)	C57Bl/6	High blood and brain Phe concentrations in line with PKU	Fewer behavioural and memory issues considering the high blood and brain Phe concentrations	²²²
	Enu-3 (ENU-induced random mutagenesis)	BTBR	High blood and brain Phe concentrations in line with PKU	Severe PKU; not available due to difficult breeding and husbandry	²⁴¹
	PAH exon 1 deletion	C57Bl/6	High blood and brain Phe concentrations in line with PKU	Behaviour not yet assessed	²⁴²
Minipig	PAH exon 6 deletion	Yucatan minipig	High blood Phe concentrations	Hypopigmentation and ventriculomegaly	²⁴³
Minipig	Humanized p.R408W PAH allele	Ossabaw minipig or Yorkshire full-size pig	High blood and brain Phe concentrations in line with PKU	Prenatal growth failure and neonatal seizures	²⁴⁴

BH4, tetrahydrobiopterin; ENU, ethylnitrosourea; HPA, hyperphenylalaninaemia; PAH, phenylalanine hydroxylase; Phe, phenylalanine; PKU, phenylketonuria.