Phenotypes Associated with This Genotype

Genotype
MGI:7628681

• Allelic Composition: Mical1^tm1.2Past/Mical1^tm1.2Past
• Genetic Background: involves: 129

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

nervous system

abnormal hippocampal mossy fiber morphology ( J:240378 )

• the characteristic lamination pattern of mossy fibers emanating from the dentate gyrus is altered; at rostral levels, mossy fibers fail to bifurcate and prematurely invade the stratum pyramidale, forming thick, fasciculated bundles that aberrantly navigate between CA3 somata

• CB+ mossy fiber density in the stratum pyramidale of CA3 is increased

abnormal hippocampal mossy fiber infrapyramidal bundle morphology ( J:240378 )

• the infrapyramidal bundle is absent or misplaced in the stratum pyramidale

• the length of both the suprapyramidal bundle and infrapyramidal bundle and the distance between them are decreased

abnormal hippocampal mossy fiber suprapyramidal bundle morphology ( J:240378 )

• more caudally, the suprapyramidal bundle is discernable but appears less compact and reduced in width, especially in CA3c

• the length of both the suprapyramidal bundle and infrapyramidal bundle and the distance between them are decreased

abnormal innervation ( J:240378 )

• the organization of the suprapyramidal bundle and stratum pyramidale is intact initially at P0-P5, however numerous axons penetrate the stratum pyramidale in between dispersed CA3 neurons from P7 onwards indicating aberrant pattern of mossy fiber innervation

abnormal neurite morphology ( J:240378 )

• growth cones of dentate gyrus neurons show an increase in F-actin in the central domain and in large bundles emanating from this region towards the growth cone membrane

abnormal synapse morphology ( J:240378 )

• mice show ectopic synapses in the stratum pyramidale; numerous synaptoporin+ mossy fiber terminals are seen around CA3 pyramidal neuron somata in the stratum pyramidale and these aberrantly located terminals form synapse-like junctions containing numerous synaptoporin+ vesicles directly on the somata of CA3 pyramidal neurons or on large and branched spine-like structures emanating from the soma, often forming multiple postsynaptic densities

• 21 days in vitro (DIV) hippocampal neurons show an increase in the number of synaptoporin+;vGlut1+ puncta on CA3 somata indicating increased synapse formation on CA3 somata

• 21 DIV co-cultures of dentate gyrus neurons from mutant mice make more synaptic contacts onto wild-type CA3 somata as compared with wild-type dentate gyrus neurons

abnormal synaptic vesicle morphology ( J:240378 )

• the number of Rab6 secretory vesicles in the growth cone of dentate gyrus neurons grown in culture is increased and many vesicles accumulate in areas of abnormal F-actin expression

cellular

abnormal cell morphology ( J:240378 )

• mouse embryonic fibroblasts (MEFs) display a compact, round morphology instead of the normal fibroblast-like irregular shape and are smaller

• MEFs exhibit strongly bundled F-actin and increased amount of peripheral F-actin

• MEFs show an increase in the number of Rab6 vesicles at the cell periphery in areas of dense F-actin bundles, however overall density of Rab6 vesicles is unchanged

abnormal synaptic vesicle morphology ( J:240378 )

• the number of Rab6 secretory vesicles in the growth cone of dentate gyrus neurons grown in culture is increased and many vesicles accumulate in areas of abnormal F-actin expression