Phenotypes Associated with This Genotype

Genotype
MGI:3721424

• Allelic Composition: Cdk5r1^tm1Lht/Cdk5r1^tm1Lht
• Genetic Background: involves: 129S4/SvJae

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

mortality/aging

premature death ( J:38857 )

nervous system

seizures ( J:38857 )

abnormal axon extension ( J:193542 )

• neurons fail to respond to BDNF treatment with increased spine density unlike wild-type cells

abnormal forebrain morphology ( J:38857 )

• mice on 129 inbred background show the phenotypes observed on the mixed 129Sv/C57BL/6 background

abnormal forebrain development ( J:38857 )

abnormal olfactory bulb development ( J:38857 )

dilated lateral ventricle ( J:38857 )

decreased corpus callosum size ( J:38857 , J:204269 )

• size of the corpus callosum is severely reduced (J:204269)

abnormal striatum morphology ( J:38857 )

abnormal hippocampus morphology ( J:38857 )

abnormal dentate gyrus morphology ( J:38857 )

abnormal hippocampus layer morphology ( J:38857 )

abnormal cerebral cortex morphology ( J:38857 )

abnormal stratification in cerebral cortex ( J:204269 )

• lamination of the cerebral cortex is abnormal

ectopic Purkinje cell ( J:38857 )

abnormal cerebellar molecular layer ( J:38857 )

abnormal innervation ( J:204269 )

• 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

reduced long-term potentiation ( J:193542 )

• following application of BDNF

behavior/neurological

abnormal behavioral response to xenobiotic ( J:204269 )

• 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

abnormal sensitization to xenobiotic ( J:204269 )

• 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

hyperactivity ( J:204269 )

• mice show hyperactivity over a 60-minute testing period compared with controls

seizures ( J:38857 )

cellular

abnormal axon extension ( J:193542 )

• neurons fail to respond to BDNF treatment with increased spine density unlike wild-type cells

increased cellular glucose import ( J:204269 )

• mice show a greater rate of glucose uptake in the cerebral cortex

homeostasis/metabolism

increased serotonin level ( J:204269 )

• mice exhibit small, but significant, elevations in basal serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels

abnormal physiological response to xenobiotic ( J:204269 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
attention deficit hyperactivity disorder		DOID:1094	OMIM:143465 OMIM:608903 OMIM:608904 OMIM:608905 OMIM:608906 OMIM:612311 OMIM:612312	J:204269