Phenotypes associated with this allele

• Allele Symbol: Pah^em1Coha
• Allele Name: endonuclease-mediated mutation 1, Cary O Harding
• Allele ID: MGI:8345745
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pah^em1Coha/Pah^em1Coha	C57BL/6NJ-Pah^em1Coha	MGI:8345880
ht2	Pah^em1Coha/Pah^+	C57BL/6NJ-Pah^em1Coha	MGI:8345883

Genotype
MGI:8345880

hm1

• Allelic Composition: Pah^em1Coha/Pah^em1Coha
• Genetic Background: C57BL/6NJ-Pah^em1Coha

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

lethality at weaning, incomplete penetrance ( J:380540 )

• mice struggle to wean from nursing to solid food, with increased mortality at weaning

pigmentation

diluted coat color ( J:380540 )

• mice that survive beyond weaning exhibit coat color hypopigmentation on an unrestricted diet

behavior/neurological

abnormal eating behavior ( J:380540 )

• mice struggle to wean from nursing to solid food

homeostasis/metabolism

decreased circulating tyrosine level ( J:380540 )

• serum tyrosine levels are lower in 6-12-week-old mice

increased phenylalanine level ( J:380540 )

• brain phenylalanine content is elevated

• however, no differences in brain tyrosine or tryptophan content

• mice treated with liver tropic recombinant adeno-associated virus serotype 8 containing murine Pah cDNA gene-therapy exhibit substantial correction of phenylalanine levels in the brain 14 days post-administration

increased circulating phenylalanine level ( J:380540 )

• serum phenylalanine levels are elevated in 6-12-week-old mice

• mice treated with liver tropic recombinant adeno-associated virus serotype 8 containing murine Pah cDNA gene-therapy exhibit substantial correction of phenylalanine levels in the blood 14 days post-administration

decreased serotonin level ( J:380540 )

• brain serotonin and 5-HIAA content is decreased

• however, brain dopamine levels are normal

abnormal enzyme/coenzyme activity ( J:380540 )

• PAH enzymatic activity is undetectable in the liver

• mice treated with murine Pah gene-therapy exhibit liver PAH enzyme activity

integument

diluted coat color ( J:380540 )

• mice that survive beyond weaning exhibit coat color hypopigmentation on an unrestricted diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
phenylketonuria		DOID:9281	OMIM:261600	J:380540

Genotype
MGI:8345883

ht2

• Allelic Composition: Pah^em1Coha/Pah⁺
• Genetic Background: C57BL/6NJ-Pah^em1Coha

homeostasis/metabolism

increased nervous system dopamine level ( J:380540 )

• brain levels of the dopamine metabolite homovanillic acid (HVA) is increased

increased serotonin level ( J:380540 )

• brain serotonin is somewhat increased but only 3 mice were analyzed

abnormal enzyme/coenzyme activity ( J:380540 )

• PAH enzymatic activity is 58% that of wild-type activity

nervous system

increased nervous system dopamine level ( J:380540 )

• brain levels of the dopamine metabolite homovanillic acid (HVA) is increased