Mouse Genome Informatics
hm1
    Pitx3ak/Pitx3ak
either: (involves: 129/Sv * C57BLKS) or (involves: 129/Sv * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• intensly pigmented around the pupil at E13
• pupillary area replaced by iris at E17-18

behavior/neurological
• reduced spontaneous activity at night

endocrine/exocrine glands
• enlarged lacrimal gland partially fills the orbit

growth/size
• slightly smaller than normal

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

vision/eye
• enlarged lacrimal gland partially fills the orbit
• intensly pigmented around the pupil at E13
• pupillary area replaced by iris at E17-18
• no pupil at birth
• little growth or organization of the lens vesicle after E11
• ocular area slightly concave after eyes open
• eyes slightly smaller than normal at birth
• slightly smaller and uneven at E13
• abnormal growth of the eyecup after E13
• sensory and pigmented layers remain separated
• many retinal folds at birth
• partially fills the vitreous chamber

nervous system
• 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)
• less cellularity in the substantia nigra
• tyrosine hydroxylase immunoreactivity absent in the substantia nigra
• decreased numbers of nigrostriatal fibers

Mouse Models of Human Disease
OMIM IDRef(s)
Anterior Segment Mesenchymal Dysgenesis; ASMD 107250 J:5084 , J:82746 , J:82907


Mouse Genome Informatics
hm2
    Pitx3ak/Pitx3ak
involves: 129S1/Sv * C57BL/6 * C57BLKS/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• levels are reduced to 10% of wildtype in the dorsal striatum, however levels in the ventral striatum are not affected
• 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
• 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
• selective loss of A9 dopaminergic neurons in the substantia nigra; A10 neurons in the ventral tegmental area appear to be intact

behavior/neurological
• 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
• higher ambulatory activity than control during lights-on period, however, lower ambulatory activity than control during lights-off period
• 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
• total horizontal movements during a 22 hour period are slightly increased over that of control

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