All Phenotypes Kif5a<tm1Gsn> MGI Mouse

lethality at weaning, incomplete penetrance ( J:82911 )

• 72% of mutant mice die of seizures at ~3 weeks of age, between P15 and P25

premature death ( J:82911 )

• the remaining ~28% (8 of 29) of mutant mice survived to >3 months of age; one died at 3 months, one at 4 months, and another at 5.5 months, while the rest were sacrified at 5.5, 7, and 8 months

decreased body size ( J:82911 )

• by 2-3 weeks of age, mutant mice are obviously smaller than control littermates

decreased body weight ( J:82911 )

• at 3 weeks of age, mutant body weight is only ~50% of control weight

tremors ( J:82911 )

• at 3 weeks of age, mutant mice frequently display a tremor, although their posture is relatively normal

• all mutant mice surviving to >5 months of age, develop tremors while walking

impaired coordination ( J:82911 )

• at 3 weeks of age, mutant mice fall off the rotarod more frequently than control mice

abnormal posture ( J:82911 )

• all mutant mice surviving to >5 months of age develop abnormal hindlimb posture at rest

• however, a relatively normal posture is observed until ~5 months of age

hindlimb paralysis ( J:82911 )

• mutant mice surviving to >5 months of age develop a partial hindlimb paralysis

sporadic seizures ( J:82911 )

• 72% of mutant mice die from spontaneous seizures lasting 20-30 seconds

• repetitive seizures and stress-induced seizures are also observed

sporadic seizures ( J:82911 )

• 72% of mutant mice die from spontaneous seizures lasting 20-30 seconds

• repetitive seizures and stress-induced seizures are also observed

axon degeneration ( J:82911 )

• mutant mice surviving to >5 months of age display a striking degeneration of sensory axons within L5 lumbar dorsal roots along with numerous profiles of myelin debris

• at 3 weeks of age, mutants show a ~14% loss of sensory axon numbers within L5 dorsal roots, with a preferrential (60%) loss of large caliber sensory axons (>3 m in diameter) but no significant loss of small caliber axons

• by 5.5 months of age, mutants exhibit a ~12% loss of motor axons and a profound 36% loss of sensory axons; again, sensory and motor axon loss is most severe for large caliber axons (>4 m), and loss of ventral root axons is not as profound as that observed in the dorsal root

• at 5.5 months of age, the peak of the distribution of the diameter of large caliber axons in the ventral root shifts from 7-7.5 m in controls to 5.5-6 m in mutants

• in the dorsal roots, severe axon loss is noted in sensory axons with calibers >2 m, with complete loss of the largest sensory axons (>7 m), but no loss of small caliber sensory axons (<1.5 m)

abnormal axonal transport ( J:82911 )

• at 3 weeks of age, mutant mice show a a specific deficit in the slow axonal transport of neurofilaments, as evidenced by the accumulation of NF subunits (NF-H, NF-L, and NF-M) and peripherin in the cell bodies of DRG sensory neurons

• however, no obvious changes in the amounts of NF-H, NF-M, NF-L, or peripherin are detected in the brain and sciatic nerve of mutant mice

• in addition, fast axonal transport appears to be intact, as markers of several fast axonal transport pathways (APP, Rab3, and synaptophysin) appeared unchanged in the DRG and in sciatic nerve ligation experiments

abnormal protein level ( J:82911 )

• at 3 weeks of age, mutant mice display a striking accumulation of neurofilament (NF) subunits (NF-H, NF-L, and NF-M) and peripherin in the cell bodies of dorsal root ganglion (DRG) sensory neurons, due to a specific deficit in slow axonal transport of NFs

• neurofilament accumulation in the DRG is accompanied by a significant decrease in the number of large caliber sensory axons

• betaIII-tubulin is unchanged in younger animals, but displays behavior indicative of defective transport in some older mutant mice

• notably, accumulation of NF subunit levels in the DRG is not accompanied by obvious reductions in the sciatic nerve

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

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

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

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support.	last database update 11/12/2024 MGI 6.24