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Phenotypes Associated with This Genotype
Genotype
MGI:5647883
Allelic
Composition
Lmx1atm1Tpe/Lmx1atm1Tpe
Lmx1btm1Zfc/Lmx1btm1Zfc
Slc6a3tm1(cre)Lrsn/Slc6a3+
Genetic
Background
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmx1atm1Tpe mutation (0 available); any Lmx1a mutation (20 available)
Lmx1btm1Zfc mutation (0 available); any Lmx1b mutation (16 available)
Slc6a3tm1(cre)Lrsn mutation (1 available); any Slc6a3 mutation (66 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• novel object recognition test indicates impaired short-term memory formation in adult and aged mice
• however, no differences are seen in anxiety or depression-like tests
• impaired motor coordination in the pole test at 6 months of age and in the beam traversal and pole test at 18 months of age
• in the open field, mice show a modest increase in locomotor activity at 18, but not 6, months of age

nervous system
• midbrain dopamine neuron innervation is impaired
• treatment with rapamycin almost completely normalizes the reduced striatal TH innervation
• 3 month old mice exhibit abnormal nerve terminals in the striatum, with a 50% reduction in the density of TH-positive nerve terminals and abnormally large nerve terminals that reach up to 22 um in diameter frequently throughout the dorsal and ventral striatum
• enlarged presynaptic boutons show fewer synaptic vesicles at active zones and are filled with vacuoles and multilamellar autophagic-lysosomal vesicles that sometimes contain mitochondria
• 23% lower occurrence of synaptic active zones
• treatment with rapamycin alleviates the occurrence of abnormally large TH+ boutons in the striatum
• synaptic morphology is disrupted in presynaptic midbrain dopamine neuron terminals
• enlarged presynaptic boutons show fewer synaptic vesicles at active zones
• progressive loss of TH-positive neurons in the ventral midbrain, with degenerating TH+ neurons frequently seen in young mice; reduction is seen within both the dorsal and ventral striatum
• dopamine transporter (DAT) expression is reduced, showing a modest reduction in young mice but a significant reduction in aged mice, indicating dopaminergic neuron degeneration
• mice exhibit enhanced induced LTP of Shaffer collateral-CA1 pyramidal cell synapses
• however, basal synaptic transmission is normal

taste/olfaction
• social olfaction is impaired in adult (6 months) and aged (18 months) mice

cellular
• accumulation of lysosomes in axonal terminals of midbrain dopamine neurons
• accumulation of autophagosomes in axonal terminals of midbrain dopamine neurons
• the number of lipofuscin granules are reduced in midbrain dopamine neurons
• accumulation of electron-dense protein aggregates in midbrain dopamine neuron cell bodies

homeostasis/metabolism
• accumulation of autophagosomes in axonal terminals of midbrain dopamine neurons
• dopamine and its metabolites are reduced in brain areas such as prefrontal cortex, hippocampus, dorsal striatum, nucleus accumbens, substantia nigra and the ventral tegmental area
• however, levels are not reduced in the olfactory bulb or the cerebellum

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Parkinson's disease DOID:14330 OMIM:PS168600
J:222854


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/12/2024
MGI 6.23
The Jackson Laboratory