Phenotypes Associated with This Genotype

Genotype
MGI:6241436

• Allelic Composition: Kif21a^tm1.1Ece/Kif21a^tm1.1Ece; Tg(Isl1-EGFP*)1Slp/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * BALB/c * C57BL/6

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

vision/eye

abnormal extraocular muscle morphology ( J:213171 )

• extraocular muscle hypoplasia begins after P0, several days after extraocular muscle innervation is reduced, with normal position and size of the superior rectus and superior rectus muscles at E14.5

nervous system

increased neuron apoptosis ( J:213171 )

• oculomotor nerve neurons show increased apoptosis from E12.5-E15.5

abnormal axon extension ( J:213171 )

• oculomotor nerve neurons show failure of axon elongation to the orbit; this nerve growth failure precedes motor neuron apoptosis

• developing axons of the oculomotor nerves superior division stall in the proximal nerve, and the growth cones enlarge, extend excessive filopodia, and assume random trajectories while inferior division axons reach the orbit but branch ectopically

abnormal axon morphology ( J:213171 )

• oculomotor explant axons have normal growth but enlarged growth cones and increased filopodia

abnormal abducens nerve morphology ( J:213171 )

• the distal abducens nerves appear thin at E12.5 and are thinner at E15.5

abnormal oculomotor nerve morphology ( J:213171 )

• oculomotor nerve superior branch axons terminate prematurely within a bulb; the bulb contains misdirected axons with enlarged growth cones and increased number of filopodia and degenerating axons

• the developing distal oculomotor nerve superior division is hypoplastic while the inferior division develops aberrant branches

• the oculomotor nerve distal sections contain 55% fewer axons than proximal sections, and the proximal sections contain 18% fewer axons than wild-type proximal sections

• oculomotor nerve pathology does not arise from a primary defect in extraocular muscle development, axon retraction, or motor neuron cell death

thin oculomotor nerve ( J:213171 )

• thinning of distal oculomotor nerves at E11.5

• the developing oculomotor nerves superior division is thinner than that of wild-type mice, while the oculomotor nerves inferior division appears moderately thinner, with premature fasciculation into transient aberrant branches

muscle

abnormal extraocular muscle morphology ( J:213171 )

• extraocular muscle hypoplasia begins after P0, several days after extraocular muscle innervation is reduced, with normal position and size of the superior rectus and superior rectus muscles at E14.5

cellular

increased neuron apoptosis ( J:213171 )

• oculomotor nerve neurons show increased apoptosis from E12.5-E15.5

abnormal axon extension ( J:213171 )

• oculomotor nerve neurons show failure of axon elongation to the orbit; this nerve growth failure precedes motor neuron apoptosis

• developing axons of the oculomotor nerves superior division stall in the proximal nerve, and the growth cones enlarge, extend excessive filopodia, and assume random trajectories while inferior division axons reach the orbit but branch ectopically

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital fibrosis of the extraocular muscles		DOID:0080143	OMIM:PS135700	J:213171