Phenotypes Associated with This Genotype

Genotype
MGI:4850044

• Allelic Composition: Abl1^tm2.1Goff/Abl1^tm2.1Goff; Abl2^tm1Ajk/Abl2^tm1Ajk; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * SJL

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:166211 )

• recovered at a frequency (20.5%) slightly less than the expected Mendelian ratio at two weeks of age

nervous system

decreased cerebellar granule cell precursor proliferation ( J:166211 )

• reduced number of proliferating granule cell precursors (GCPs) in the secondary fissure in the posterior cerebellum at P8

• loss of proliferating GCPs is concentrated in areas where the basement membrane (BM) is disrupted

• normal proliferation of GCPs in the cerebella-derived culture

abnormal brain morphology ( J:166211 )

• scores of granule cell precursors (GCPs) abnormally protrude into the subarachnoid space between the midbrain and cerebellum at E17

• laminin-labeled basement membrane (BM) is fragmented at E15 and E17

• loss of the pial BM in the cerebellum starting from around P8

abnormal cerebellum morphology ( J:166211 )

• reduced anterior-posterior extent of the mutant adult cerebellum

• basic laminar structure of the anterior cerebellum, encompassing lobules I-V, is completely lost

abnormal cerebellar lobule formation ( J:166211 )

• obvious defects in the organization of anterior lobules I-V in P7 and P1 cerebella

reduced cerebellar foliation ( J:166211 )

• adjacent lobules, such as lobules VIII and IX, are fused

abnormal cerebellum white matter morphology ( J:166211 )

• patches of granule cells are randomly scattered throughout the white matter

abnormal cerebellar layer morphology ( J:166211 )

ectopic Bergmann glia cells ( J:166211 )

• abnormal Bergmann glial network correlates with breaches of the BM in the cerebellum at P8

• highly disorganized radial glial processes, with some of their endfeet protruding into the meninges in the mutant cerebellum at E15

ectopic Purkinje cell ( J:166211 )

• loosely aligned Purkinje cells, with some abnormally distributing at the cerebellar surface at P1

ectopic cerebellar granule cells ( J:166211 )

• GCPs ectopically embed within the cortex at P1

• ectopic granule cell differentiation near the broken BM at P8

• many granule cells ectopias at the cerebellar surface in the posterior regions of adult cerebella and along the fusion lines of adjacent lobules

• normal extent of migration of granule cells and granule cell-glia interactions at P10 before the loss of the BM

abnormal cerebellum fissure morphology ( J:166211 )

• decreased depth of the fissures

absent cerebellum fissure ( J:166211 )

• both the cerebellar vermis and the two lateral hemispheres lack clear fissures on the surface

absent cerebellar lobules ( J:166211 )

• disappearance of lobules IV and V in the anterior vermis

small cerebellum ( J:166211 )

• smaller cerebellum in adult mice

behavior/neurological

impaired coordination ( J:166211 )

• take approximately twice as long to cross the elevated balance beam

• dramatic increase in the number of foot slips

cellular

decreased cerebellar granule cell precursor proliferation ( J:166211 )

• reduced number of proliferating granule cell precursors (GCPs) in the secondary fissure in the posterior cerebellum at P8

• loss of proliferating GCPs is concentrated in areas where the basement membrane (BM) is disrupted

• normal proliferation of GCPs in the cerebella-derived culture