Phenotypes associated with this allele

• Allele Symbol: Pitx3^ak
• Allele Name: aphakia
• Allele ID: MGI:1856667
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pitx3^ak/Pitx3^ak	either: (involves: 129/Sv * C57BLKS) or (involves: 129/Sv * C57BL/6)	MGI:3042029
hm2	Pitx3^ak/Pitx3^ak	involves: 129S1/Sv * C57BL/6 * C57BLKS/J	MGI:3712364

Genotype
MGI:3042029

hm1

• Allelic Composition: Pitx3^ak/Pitx3^ak
• Genetic Background: either: (involves: 129/Sv * C57BLKS) or (involves: 129/Sv * C57BL/6)

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

pigmentation

abnormal iris pigmentation ( J:5084 )

• intensly pigmented around the pupil at E13

• pupillary area replaced by iris at E17-18

behavior/neurological

decreased locomotor activity ( J:82907 )

• reduced spontaneous activity at night

endocrine/exocrine glands

enlarged lacrimal gland ( J:5084 )

• enlarged lacrimal gland partially fills the orbit

growth/size/body

decreased body size ( J:5084 )

• slightly smaller than normal

reproductive system

reduced fertility ( J:5084 )

• fertility is reduced at generation F3 and beyond, particularly for females

vision/eye

enlarged lacrimal gland ( J:5084 )

• enlarged lacrimal gland partially fills the orbit

abnormal anterior eye segment morphology ( J:5084 )

abnormal iris pigmentation ( J:5084 )

• intensly pigmented around the pupil at E13

• pupillary area replaced by iris at E17-18

acoria ( J:5084 )

• no pupil at birth

abnormal lens development ( J:5084 )

• little growth or organization of the lens vesicle after E11

abnormal eye distance/ position ( J:5084 )

• ocular area slightly concave after eyes open

microphthalmia ( J:5084 )

• eyes slightly smaller than normal at birth

• slightly smaller and uneven at E13

abnormal posterior eye segment morphology ( J:5084 )

abnormal ocular fundus morphology ( J:5084 )

• abnormal growth of the eyecup after E13

• sensory and pigmented layers remain separated

abnormal retina morphology ( J:5084 )

• partially fills the vitreous chamber

retina fold ( J:5084 )

• many retinal folds at birth

nervous system

abnormal midbrain morphology ( J:82746 , J:82907 )

• at E12.5, mesencephalon dopaminergic neurons are normal (J:82907)

• by the first day after birth there is a 91% reduction in neurons with tyrosine hydroxylase immunoreactivity (J:82907)

• reduced activity in the ventral tegmental area but slower to develop (J:82907)

• dorsal tier of the pars compacta of the substantia nigra retains tyrosine hydroxylase activity (J:82907)

decreased substantia nigra size ( J:82746 )

• less cellularity in the substantia nigra

• tyrosine hydroxylase immunoreactivity absent in the substantia nigra

• decreased numbers of nigrostriatal fibers

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
anterior segment dysgenesis		DOID:0060648	OMIM:PS107250	J:5084 , J:82746 , J:82907

Genotype
MGI:3712364

hm2

• Allelic Composition: Pitx3^ak/Pitx3^ak
• Genetic Background: involves: 129S1/Sv * C57BL/6 * C57BLKS/J

nervous system

abnormal substantia nigra pars compacta morphology ( J:109319 )

• Nissl staining indicates that cell density is dramatically reduced in the substantia nigra pas compacta as compared to wild-type

• dopaminergic neurons remaining in the substantia nigra pars compacta appear atrophic with somewhat shrunken cell bodies

• results using both the key dopamine neuronal marker, TH, and Fluorogold retrograde labeling suggest the absence of dopaminergic neurons in the substantia nigra pas compacta indicating that nigrostriatal projections do not develop

• neuron loss is apparent in newborn mice

abnormal dorsal striatum morphology ( J:109319 )

• results using the key dopamine neuronal marker, TH, suggest a reduction of neurons in the dorsal striatum, however, not in the nucleus accumbens or olfactory tubercle implying a defective nigrostriatal pathway

loss of dopaminergic neurons ( J:109319 )

• selective loss of A9 dopaminergic neurons in the substantia nigra; A10 neurons in the ventral tegmental area appear to be intact

behavior/neurological

impaired coordination ( J:98209 )

• mice exhibit longer times to traverse a balance beam challenge and a 25% increase in the number of steps as compared to controls, however, administration of L-DOPA reduced beam time and step number almost to wild-type levels

• in a vertical pole test, mice take longer than controls to orient downwards; L-DOPA administration reduces orientation time

abnormal locomotor behavior ( J:98209 )

• higher ambulatory activity than control during lights-on period, however, lower ambulatory activity than control during lights-off period

decreased vertical activity ( J:98209 )

• mice exhibit a decrease in rearing and hindlimb stepping as measured in the transparent cylinder, however, administration of L-DOPA increases spontaneous activity to the same or higher than wildtype

increased locomotor activity ( J:98209 )

• total horizontal movements during a 22 hour period are slightly increased over that of control

homeostasis/metabolism

decreased dopamine level ( J:109319 )

• levels are reduced to 10% of wildtype in the dorsal striatum, however levels in the ventral striatum are not affected

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:98209