Phenotypes Associated with This Genotype

Genotype
MGI:5440834

• Allelic Composition: Shh^tm1Ahk/Shh^tm1Ahk; Slc6a3^tm1(cre)Xz/Slc6a3⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

mortality/aging

premature death ( J:188348 )

• at about 18 months

nervous system

loss of dopaminergic neurons ( J:188348 )

• in the the substantia nigra pars compacta at 4, 8 and 16 months

• in the ventral tegmental area at 16 months

• in the striatum at 14 months

• non cell-autonomous

decreased neuron number ( J:188348 )

• in striatal TH+ fiber density at 12 months

• in ChAT+ neurons in the striatum at 6 months

increased neuron number ( J:188348 )

• in striatal TH+ fiber density at 8 months

abnormal synaptic dopamine release ( J:188348 )

• impaired amphetamine elicited

behavior/neurological

abnormal gait ( J:188348 )

• mice exhibit increased gait length coefficient of variability at 10 months of age, and shortened time allotted for braking in each stride and increased paw angle at 11 months of age compared with wild-type mice

• however, treatment with L-DOPA and THP normalizes increased variability in stride length, THP normalizes brake stride ratio and treatment with L-DOPA normalizes alterations in paw angles

decreased locomotor activity ( J:188348 )

• at 2 to 5 months

hyperactivity ( J:188348 )

• at 7 to 12 months

hindlimb paralysis ( J:188348 )

• rapidly deteriorating locomotion activity leading to pelvic dragging followed by partial hindlimb paralysis at about 18 months

homeostasis/metabolism

decreased dopamine level ( J:188348 )

• in the ventral midbrain at 16 months

• in the striatum at 2 and 16 months

increased dopamine level ( J:188348 )

• in the ventral midbrain at 2 months

• in the striatum at 7 months