Phenotypes associated with this allele

• Allele Symbol: Spr^tm1Spo
• Allele Name: targeted mutation 1, S Paul Oh
• Allele ID: MGI:3757641
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spr^tm1Spo/Spr^tm1Spo	involves: 129 * C57BL/6	MGI:3757644

Genotype
MGI:3757644

hm1

• Allelic Composition: Spr^tm1Spo/Spr^tm1Spo
• Genetic Background: involves: 129 * C57BL/6

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

mortality/aging

premature death ( J:124817 )

• most mice die 1 to 2 months after birth with remaining mice dying 2 to 6 months after birth

homeostasis/metabolism

increased circulating phenylalanine level ( J:124817 )

• serum phenylalanine levels are increased (2732 uM compared to 63 uM in wild-type and heterozygous mice)

• however, phenylalanine levels can be rescued by oral administration of tetrahydrobiopterin

decreased circulating insulin-like growth factor I level ( J:124817 )

• insulin-like growth factor 1 levels are severely reduced compared to in wild-type mice

decreased dopamine level ( J:124817 )

• dopamine levels are reduced 10-fold in the caudate putamen and cortex compared to in wild-type mice

• 3,4 dihydroxyphenylacetate (DOPAC) levels in the caudate putamen and cortex are below detectable limits unlike in wild-type mice

decreased noradrenaline level ( J:124817 )

• norepinepherine levels in the cortex and cerebellum are reduced

abnormal enzyme/coenzyme level ( J:124817 )

• sepiapterin accumulation is observed in the brain and liver

abnormal biopterin level ( J:124817 )

• tetrahydrobiopterin levels are decreased in the brain (to 40.5% of wild-type levels) and liver (to 1.1% of wild-type levels)

abnormal neopterin level ( J:124817 )

• neopterin levels are increased moderately in the liver and brain by 3 and 5 times, respectively, as much as in wild-type mice

decreased serotonin level ( J:124817 )

• however, 5-hydroxyindoleacetic acid levels are normal

• serotonin levels in the cortex are reduced compared to in wild-type mice

nervous system

abnormal dopaminergic neuron morphology ( J:124817 )

• tyrosine hydrolase (TH) staining in dopaminergic cells gradually becomes faint along dopaminergic fibers and disappears in the caudate putamen unlike in wild-type mice

• almost no nerve fibers stain positive for TH in the striatum

• however, dopaminergic neurons are present

abnormal synaptic neurotransmitter level ( J:124817 )

• brain levels of dopamine, norepinepherine and serotonine are reduced compared to in wild-type mice

growth/size/body

postnatal growth retardation ( J:124817 )

• within a few days of birth mice exhibit a severe growth retardation and gain almost no weight after 2 weeks of age

• however, growth retardation and other phenotypes (such as phenylalanine levels) can be rescued by oral administration of tetrahydrobiopterin

behavior/neurological

abnormal locomotor activation ( J:124817 )

• mice score worse than wild-type mice on four-limb akinesia and turning tests