Phenotypes Associated with This Genotype

Genotype
MGI:6260058

• Allelic Composition: Dhtkd1^tm1Zgwg/Dhtkd1^tm1Zgwg
• Genetic Background: involves: C57BL/6

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

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:267178 )

• 6 month old mice, but not 6 week old mice, tend to show decreases in retention time on the rotarod due to weak muscle strength

increased thermal nociceptive threshold ( J:267178 )

• mice exhibit reduced pain sensitivity as shown by a longer response time to hot stimulus in a hot plate test

impaired exercise endurance ( J:267178 )

• 6 month old mice, but not 6 week old mice, tend to show a decrease in running distance in the treadmill test

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:267178 )

• insulin in islets is elevated

increased insulin secretion ( J:267178 )

• insulin in islets in elevated

homeostasis/metabolism

impaired exercise endurance ( J:267178 )

• 6 month old mice, but not 6 week old mice, tend to show a decrease in running distance in the treadmill test

increased insulin secretion ( J:267178 )

• insulin in islets in elevated

decreased circulating glucose level ( J:267178 )

• mice exhibit lower glucose in an insulin tolerance test

• lower glucose is due to increased insulin secretion and increased insulin sensitivity

increased circulating insulin level ( J:267178 )

• mice exhibit elevated serum insulin levels under either fasting or refed conditions

• mice show increased insulin levels during a glucose tolerance test

increased circulating insulin-like growth factor I level ( J:267178 )

increased circulating creatine kinase level ( J:267178 )

increased circulating lactate dehydrogenase level ( J:267178 )

improved glucose tolerance ( J:267178 )

• mice show increased glucose tolerance in an intraperitoneal glucose tolerance test

increased liver glycogen level ( J:267178 )

increased insulin sensitivity ( J:267178 )

aciduria ( J:267178 )

• urine 2-ketoadipic acid (2-KAA) levels are greatly increased in 16 week old mice

• urine 2-aminoadipic acid (2-AAA) levels are increased up to 120 times higher in 16 week old mutant mice than in wild-type mice

liver/biliary system

increased liver glycogen level ( J:267178 )

muscle

abnormal sarcomere morphology ( J:267178 )

• sarcomere disorder or disappearance

muscular atrophy ( J:267178 )

• muscle atrophy in the distal parts of limbs

• gastrocnemius muscle shows elevated levels of atrophy-associated markers

progressive muscle weakness ( J:267178 )

• 6 month old mice, but not 6 week old mice, tend to show decreases in retention time on the rotarod and a decrease in running distance in the treadmill test, indicating weakened muscle strength

nervous system

abnormal nervous system morphology ( J:267178 )

• mice develop peripheral neuropathy

increased Schwann cell number ( J:267178 )

abnormal myelin sheath morphology ( J:267178 )

• sciatic nerves show irregular myelin sheath that becomes dissociated from axons

abnormal neuromuscular synapse morphology ( J:267178 )

• mice exhibit an increase in the percentage of denervated neuromuscular junctions in gastrocnemius muscle

abnormal sciatic nerve morphology ( J:267178 )

• sciatic nerves show reduced large myelinated fibers, loss of distal axons, increased aberrant myelin with unchanged fiber area and thickness of the myelin sheath, and decreased density of nerve fibers

axon degeneration ( J:267178 )

• 6 month old mice show axon degeneration in sciatic nerves

• 6 week old mice mice challenged with acrylamide, an axonal neurotoxin that accelerates the progress of preexisting axonal degeneration, show decreased retention time on the rotarod and most mice treated with acrylamide fall off the rotarod even in the pretraining process, indicating that mice have axonal nerve damage

abnormal Schwann cell physiology ( J:267178 )

• marker analysis indicates that Schwann cells are functionally impaired

demyelination ( J:267178 )

• 6 month old mice show myelin sheath degeneration in sciatic nerves

decreased nerve conduction velocity ( J:267178 )

• motor nerve conduction and sensory nerve conduction velocity are decreased in the sciatic nerves of 6 month old mice

renal/urinary system

aciduria ( J:267178 )

• urine 2-ketoadipic acid (2-KAA) levels are greatly increased in 16 week old mice

• urine 2-aminoadipic acid (2-AAA) levels are increased up to 120 times higher in 16 week old mutant mice than in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Charcot-Marie-Tooth disease axonal type 2Q		DOID:0110170	OMIM:615025	J:267178