Phenotypes associated with this allele

• Allele Symbol: Shh^tm1Ahk
• Allele Name: targeted mutation 1, Andreas H Kottmann
• Allele ID: MGI:5440762
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Shh^tm1Ahk/Shh^tm1Ahk	B6.Cg-Shh^tm1Ahk	MGI:5440835
cn2	Shh^tm1Ahk/Shh^tm1Ahk Slc6a3^tm1(cre)Xz/Slc6a3^+	involves: 129S1/Sv * C57BL/6	MGI:5440834

Genotype
MGI:5440835

hm1

• Allelic Composition: Shh^tm1Ahk/Shh^tm1Ahk
• Genetic Background: B6.Cg-Shh^tm1Ahk

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

normal phenotype

no abnormal phenotype detected ( J:188348 )

• mice are born alive, are fertile and have a normal life span with no signs of any overt morphological and functional phenotype

Genotype
MGI:5440834

cn2

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

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