All Phenotypes Dok6<tm1.1Pnxi> MGI Mouse

impaired balance ( J:345844 )

• at P60, mice require significantly more time to cross the horizontal bar in a beam balance test, exhibit a reduced duration on the coat hanger after being placed in the middle of the lower horizontal bar, and show a significant decrease in rotarod residence/stay time before falling in the rotarod test

decreased grip strength ( J:345844 )

• at P60, mice show a significant reduction in forelimb grip strength

increased thermal nociceptive threshold ( J:345844 )

• at P60, the latency to the onset of hindpaw licking or shaking is significantly increased at 48-, 50- and 52 degrees Celsius in the hot plate test

impaired exercise endurance ( J:345844 )

• at P60, mice exhibit a significant reduction in treadmill lane distance in a treadmill assay

abnormal myelin sheath morphology ( J:345844 )

• as early as P7, the sciatic nerve shows major signs of myelin sheath degradation or misfolded myelin

• at P14, myelin sheaths are generally not compact and exhibit myelin fragments, onion-like and comma-shaped outfolding configurations, and splitting of the myelin lamellae with dense degeneration

• percentage of sciatic nerve axonal myelin abnormalities is significantly elevated at P7 and P14

decreased myelin sheath amount ( J:345844 )

• at P7, myelin labeled by MBP staining is significantly reduced in the sciatic nerve

increased myelin sheath thickness ( J:345844 )

• at P14, the average g-ratio in sciatic axons and the relationship between the g-ratio and sciatic nerve axon diameter are significantly decreased, suggesting that average myelin thickness is increased

axon degeneration ( J:345844 )

• at P7 and P14, TEM analysis shows typical features of axonal degeneration in the sciatic nerve, including splitting of the myelin sheath, dense cytoplasm with vacuoles, and distorted lamellae separated from the axonal membrane, similar to those observed in Dok6^tm1.2Pnxi homozygotes

• at P7, immunostaining for SMI32 (a marker of damaged axons) shows a significantly increased number of SMI32+ axons in the sciatic nerve while expression of acetylated alpha-tubulin (a marker of stable microtubules) is specifically decreased in the sciatic nerve, with no apparent change in alpha-tubulin and acetylated alpha-tubulin levels found in spinal cord or brain tissues

abnormal myelination ( J:345844 )

• percentage of myelinated axons in the sciatic nerve is significantly reduced at P7 but normal at P14, with no significant change in total axon number seen at P7 or P14

abnormal action potential ( J:345844 )

• at P60, mice show significantly decreased nerve conduction velocity (NCV) and severely reduced amplitudes of the compound action potentials (CAPs) in the sciatic nerve, indicating severe axonal damage

decreased nerve conduction velocity ( J:345844 )

• at P60, mice exhibit a significant reduction in nerve conduction velocity (NCV) in the sciatic nerve

abnormal axonal transport ( J:345844 )

• analysis of retrograde axonal transport using the AF488-CTB tracer shows accumulation of fluorescent signaling endosomes in specific segments of the teased sciatic nerve and a delayed transfer process with AF488-CTB segmental accumulation and discontinuous appearance in sciatic nerve axons

impaired exercise endurance ( J:345844 )

• at P60, mice exhibit a significant reduction in treadmill lane distance in a treadmill assay

♀	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)
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