Phenotypes Associated with This Genotype

Genotype
MGI:2175756

• Allelic Composition: Cdk5r1^tm1Lht/Cdk5r1^tm1Lht
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

mortality/aging

premature death ( J:38857 )

• ~15% of homozygotes die by ~4 months, starting at about 3 weeks of age

nervous system

seizures ( J:38857 )

• over long-term observation, seizures are observed

increased susceptibility to pharmacologically induced seizures ( J:38857 )

• administration of 50 mg/kg pentylenetetrazol, induces generalized convulsions (with loss of posture, myclonic jerks, hyperextension of neck and trunk associated with cycling motions of limbs and extension of hind limbs) in wild-type and mutant mice with similar frequency, but slightly shorter latency in mutants; >50% of mutants die within minutes of end of tonic-clonic phase of seizures, whereas no wild-type animals die

abnormal forebrain morphology ( J:38857 )

• in three-month old mice, general disorganization of forebrain is apparent

thin cortical plate ( J:38857 )

• cortical plate is 30-50% thinner than in wild-type embryos at E15

abnormal subplate morphology ( J:71181 )

• at E18.5, an ectopic cortical subplate is detected under the most superficial cortical plate with later-born cortical neurons accumulated underneath

abnormal olfactory bulb development ( J:38857 )

• internal plexiform layer between mitral cell layer and internal granule layers is absent

dilated lateral ventricle ( J:38857 )

• lateral ventricles are ~twice the size of lateral ventricles in wild-type brain in 3-month old animals

decreased corpus callosum size ( J:38857 )

• size (thickness) is significantly reduced

decreased striatum size ( J:38857 )

• size is reduced

abnormal hippocampus morphology ( J:38857 , J:71181 )

• at E18.5, hippocampus shows signs of disorganization, but this is less severe than in double null mutants (J:71181)

abnormal dentate gyrus morphology ( J:38857 )

abnormal hippocampus layer morphology ( J:38857 )

• layers II and III are occupied by large instead of small pyramidal neurons

• most cells in hippocampus and dentate gyrus are included in a laminar structure like in wild-type, but cells are less densely packed

abnormal cerebral cortex morphology ( J:38857 , J:71181 )

• laminated structure is not apparent in 3-month old mice; defects in lamination are less severe in lateral-ventral region of cortex (J:38857)

• no recognizable pattern is observed for distribution of pyramidal, granule, and polymorphic cells in cortex (J:38857)

• mutant cortex contains aberrant fascicles in the neocortex and no fascicles are seen in the lateral-ventral portion of the cortex (J:38857)

• radial distribution of pyramidal neurons and their apical dendrites is not conspicuous like in wild-type brains (J:38857)

• cortex shows mild neuronal-positioning abnormalities (J:71181)

abnormal cerebral cortex pyramidal cell morphology ( J:38857 )

• orientation of neuronal soma and direction of dendritic growth are altered; defect is more severe in medial neocortex

ectopic Purkinje cell ( J:38857 )

• some cells are located in granule cell layer

abnormal cerebellar molecular layer ( J:38857 )

• molecular layer shows a greater cell density than wild-type, and contains cells resembling granule cells

behavior/neurological

seizures ( J:38857 )

• over long-term observation, seizures are observed

increased susceptibility to pharmacologically induced seizures ( J:38857 )

• administration of 50 mg/kg pentylenetetrazol, induces generalized convulsions (with loss of posture, myclonic jerks, hyperextension of neck and trunk associated with cycling motions of limbs and extension of hind limbs) in wild-type and mutant mice with similar frequency, but slightly shorter latency in mutants; >50% of mutants die within minutes of end of tonic-clonic phase of seizures, whereas no wild-type animals die