Phenotypes Associated with This Genotype

Genotype
MGI:3712364

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

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

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