Phenotypes Associated with This Genotype

Genotype
MGI:4839271

• Allelic Composition: Tg(Nes-cre)1Kln/0; Trio^tm1Mzhu/Trio^tm1Mzhu
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

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

Growth retardation, ataxia, small brain size, and reduced olfactory bulb size in Trio^tm1Mzhu/Trio^tm1Mzhu Tg(Nes-cre)1Kln/0 mice

mortality/aging

postnatal lethality, complete penetrance ( J:165902 )

• remaining mice die between P5 and P22

neonatal lethality, incomplete penetrance ( J:165902 )

• 90% of mice die within 1 day of birth

nervous system

abnormal Bergmann glial cell morphology ( J:165902 )

• between P8 and P21 glial fibers become progressively sparse unlike in wild-type mice

increased neuron apoptosis ( J:165902 )

• in granule cells

abnormal neuron differentiation ( J:165902 )

• cerebellar granule neurons exhibit impaired neurite growth compared with wild-type cells

• neurite outgrowth is unresponsive to Netrin-1 and Semaphorin 6A induction unlike wild-type cells

• however, neurite ougrowth is normally induced by glutamate and nerve growth factor

abnormal cerebellar granule cell migration ( J:165902 )

• most granules remain outside of the Purkinje cell layer and are randomly at the external granular layer and molecular layer unlike in wild-type mice

• cultured granule cells exhibit decreased migration with random orientations along their abnormal processes compared with similarly treated wild-type mice

abnormal cerebellum external granule cell layer morphology ( J:165902 )

• parallel fibers are thick and non-compact compared to in wild-type mice

• mice lack horizontal beams of parallel fibers in the inner external granule cell layer compared with wild-type mice

abnormal rostral migratory stream morphology ( J:165902 )

• the rostral migratory stream is enlarged compared to in wild-type mice

decreased brain size ( J:165902 )

• at P21

abnormal dentate gyrus morphology ( J:165902 )

abnormal olfactory bulb mitral cell layer morphology ( J:165902 )

• indistinguishable with the internal granule cell layer

small olfactory bulb ( J:165902 )

abnormal cerebellar granule layer morphology ( J:165902 )

• at P0.5, the inner granular layer lacks granule cells compared to in wild-type mice

abnormal cerebellar granule cell morphology ( J:165902 )

• granule cells in the external granule layer exhibit disorganized cell bodies with abnormal organization of parallel fibers compared with wild-type mice

• granules exhibit short and highly branched processes, irregular growth cone with highly branched terminals, and strong filipodia in the axon shaft and the tips of leading process compared with wild-type cells

abnormal cerebellum lobule morphology ( J:165902 )

• some sub-lobules fail to form unlike in wild-type mice

• however, all lobules do form

small cerebellum ( J:165902 )

• at P0.5, P6, and P21

behavior/neurological

absent gastric milk in neonates ( J:165902 )

limb grasping ( J:165902 )

• at P21

ataxia ( J:165902 )

• at P21

growth/size/body

decreased body weight ( J:165902 )

postnatal growth retardation ( J:165902 )

cellular

abnormal Bergmann glial cell morphology ( J:165902 )

• between P8 and P21 glial fibers become progressively sparse unlike in wild-type mice

increased neuron apoptosis ( J:165902 )

• in granule cells

abnormal neuron differentiation ( J:165902 )

• cerebellar granule neurons exhibit impaired neurite growth compared with wild-type cells

• neurite outgrowth is unresponsive to Netrin-1 and Semaphorin 6A induction unlike wild-type cells

• however, neurite ougrowth is normally induced by glutamate and nerve growth factor

abnormal cerebellar granule cell migration ( J:165902 )

• most granules remain outside of the Purkinje cell layer and are randomly at the external granular layer and molecular layer unlike in wild-type mice

• cultured granule cells exhibit decreased migration with random orientations along their abnormal processes compared with similarly treated wild-type mice