Phenotypes associated with this allele

• Allele Symbol: Pts^tm1Ich
• Allele Name: targeted mutation 1, Hiroshi Ichinose
• Allele ID: MGI:2669870
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pts^tm1Ich/Pts^tm1Ich	B6.129X1-Pts^tm1Ich	MGI:2669894
hm2	Pts^tm1Ich/Pts^tm1Ich	involves: 129X1/SvJ * C57BL/6J	MGI:2669893
cx3	Pts^tm1Ich/Pts^tm1Ich Tg(DBH-PTS)6Csic/0	B6.Cg-Pts^tm1Ich Tg(DBH-PTS)6Csic	MGI:3813925
cx4	Pts^tm1Ich/Pts^tm1Ich Tg(DBH-PTS)6Csic/0	involves: 129X1/SvJ * C57BL/6J	MGI:3813927

Genotype
MGI:2669894

hm1

• Allelic Composition: Pts^tm1Ich/Pts^tm1Ich
• Genetic Background: B6.129X1-Pts^tm1Ich

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

mortality/aging

postnatal lethality, complete penetrance ( J:84764 )

• 100% mortality within the first 2 days of life

Genotype
MGI:2669893

hm2

• Allelic Composition: Pts^tm1Ich/Pts^tm1Ich
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

mortality/aging

postnatal lethality, complete penetrance ( J:84764 )

• 100% of mortality within the first 2 days of life

• repeated injections of BH4 allow for survival up to P7

cardiovascular system

decreased heart rate ( J:84764 )

• 36% fewer beats per minute than wild-type

homeostasis/metabolism

increased phenylalanine level ( J:84764 )

• accumulation of phenylalanine in the brain and liver tissues in mice where survival is prolonged by BH4 treatment

decreased dopamine level ( J:84764 )

decreased noradrenaline level ( J:84764 )

• reduced levels in the brain

abnormal biopterin level ( J:84764 )

• decreased biopterin levels in the brain

abnormal neopterin level ( J:84764 )

• increased neopterin levels in the brain

decreased serotonin level ( J:84764 )

• reduced levels in the brain

nervous system

abnormal nervous system physiology ( J:84764 )

• peripheral nervous system function is impaired

• nerve fibers but not cell bodies of dopaminergic and noradrenergic neurons show reduced expression of tyrosine hydroxylase

• sympathetic nerve terminals in the kidney have reduced levels of tyrosine hydroxylase

growth/size/body

postnatal growth retardation ( J:84764 )

• in mice given repeated BH4 injections

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
BH4-deficient hyperphenylalaninemia A		DOID:0090106	OMIM:261640	J:84764

Genotype
MGI:3813925

cx3

• Allelic Composition: Pts^tm1Ich/Pts^tm1Ich; Tg(DBH-PTS)6Csic/0
• Genetic Background: B6.Cg-Pts^tm1Ich Tg(DBH-PTS)6Csic

mortality/aging

preweaning lethality, incomplete penetrance ( J:102278 )

• fewer than expected females are found at weaning

• however, unlike homozygous mice without the transgene, mice survive past weaning

homeostasis/metabolism

decreased circulating phenylalanine level ( J:102278 )

• injection of BH4 (20 mg/kg) results in a dramatic decrease in plasma phenylalanine level, a similar injection does not alter phenylalanine levels in controls

abnormal biopterin level ( J:102278 )

• biopterin content in the liver is about 0.1% of that in wild-type controls

• biopterin levels in the striatum are reduced while levels in the midbrain are closer to those in controls

abnormal neopterin level ( J:102278 )

• neopterin levels are increased to 2980 pmol/mg protein in the liver compared to undetectable levels in wild-type controls

• neopterin levels are elevated in the brain

decreased serotonin level ( J:102278 )

• serotonin levels are low in the pons-medulla and hypothalamus

nervous system

abnormal nervous system physiology ( J:102278 )

• tyrosine hydroxylase activity is mildly decreased in the midbrain and more severely decreased in the striatum

growth/size/body

decreased body weight ( J:102278 )

• at 4 weeks of age, average body weight is about 56% that of controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dystonia		DOID:543	OMIM:PS128100	J:102278

Genotype
MGI:3813927

cx4

• Allelic Composition: Pts^tm1Ich/Pts^tm1Ich; Tg(DBH-PTS)6Csic/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

nervous system

abnormal nervous system physiology ( J:138968 )

• striatal tyrosine hydroxylase expression is markedly reduced in the caudoputamen and in the lateral part of the olfactory tubercle but not in the nucleus accumbens

• loss of tyrosine hydroxylase expression results from progressive postnatal loss of expression and failure to increase expression with maturation

abnormal neuron physiology ( J:138968 )

• responses to stimulation with a dopamine agonist suggest dopaminergic hypersensitivity in the striatum particularly in the striosomes

behavior/neurological

limb grasping ( J:138968 )

• first detected at 2 weeks of age

dystonia ( J:138968 )

• results suggest mice display hypokinetic hindlimb dystonia

impaired balance ( J:138968 )

• in balance beam tests mice are slower and make more foot slips

muscle

dystonia ( J:138968 )

• results suggest mice display hypokinetic hindlimb dystonia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dystonia		DOID:543	OMIM:PS128100	J:138968