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Phenotypes Associated with This Genotype
Genotype
MGI:3721424
Allelic
Composition
Cdk5r1tm1Lht/Cdk5r1tm1Lht
Genetic
Background
involves: 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdk5r1tm1Lht mutation (1 available); any Cdk5r1 mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

nervous system
• neurons fail to respond to BDNF treatment with increased spine density unlike wild-type cells
• mice exhibit small, but significant, elevations in basal serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels
• mice on 129 inbred background show the phenotypes observed on the mixed 129Sv/C57BL/6 background
• size of the corpus callosum is severely reduced (J:204269)
• lamination of the cerebral cortex is abnormal
• tracer analysis indicates that mutants exhibit a loss in the layer-specific afferentiation of descending medial prefrontal cortex outputs projecting to the nucleus accumbens
• mice show an increased density of dopaminergic fiber innervation in the infralimbic, prelimbic, and cingulate cortices
• following application of BDNF

behavior/neurological
• mice dosed repeatedly with psychostimulants exhibit hypolocomotion, such that by the 5th day of methylphenidate (MPH) dosing, locomotor activity is reduced to 63% of controls
• mice exhibit a hypolocomotive response to repeated injections of cocaine
• mice do not exhibit sensitized responses to MPH dosing over 5 days as seen in wild-type mice
• mice are deficient in sensitization to repeated injections of cocaine
• mice show hyperactivity over a 60-minute testing period compared with controls

cellular
• neurons fail to respond to BDNF treatment with increased spine density unlike wild-type cells
• mice show a greater rate of glucose uptake in the cerebral cortex

homeostasis/metabolism
• mice exhibit small, but significant, elevations in basal serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels
• dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), levels are reduced in the striatum and prefrontal cortex of mice dosed with MPH for 5 days, however basal levels of both are normal
• dopamine turnover is increased in response to repeated MPH treatment compared to un-treated mutants while treatment of wild-type mice with MPH has no effect on dopamine turnover
• after chronic MPH treatment, mice show about a 51% reduction in dopamine turnover compared to chronically treated wild-type mice
• chronic MPH induces a 1.08-fold increase in 5-HT, an 18% decrease in 5-HIAA, and a 23% decrease in 5-HT turnover in mutants compared to wild-type mice
• no differences are seen in the caudate putamen after MPH treatment


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
03/19/2019
MGI 6.13
The Jackson Laboratory