Phenotypes Associated with This Genotype

Genotype
MGI:3653638

• Allelic Composition: Kl^kl/Kl^kl
• Genetic Background: involves: C3H/HeJ * C57BL/6J

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

mortality/aging

premature death ( J:81240 )

• treatment of mice with the antioxidant alpha-tocopherol did not increase lifespan

behavior/neurological

abnormal contextual conditioning behavior ( J:81240 )

• at 7 weeks of age, contextual freezing is similar in tests at 1 hour after training but reduced in tests at 24 hours after training

abnormal cued conditioning behavior ( J:81240 )

• at 7 weeks of age tone-induced freezing is reduced in test 1 and 24 hours after training; however, no difference in nociceptive responses are detected

• treatment of mice with the antioxidant alpha-tocopherol restores reactions in both tests to wild-type levels

impaired long-term object recognition memory ( J:81240 )

• at 7 weeks of age retention of novel object recognition is impaired in a test 24 hours after training but not in a test 1 hour after training or in either test at 6 weeks of age

• treatment of mice with the antioxidant alpha-tocopherol restores retention in the 24 hour test to wild-type levels

nervous system

abnormal nervous system physiology ( J:81240 )

• at 6 and 8 weeks of age Cu/Zn-superoxide dismutase activity in the hippocampus is increased by 58.6% and 49.3% compared to wild-type mice

cellular

oxidative stress ( J:81240 )

• age-dependent increases in accumulation of oxidative lipid and DNA damage are seen in the hippocampus and cerebral cortex

• treatment of mice with the antioxidant alpha-tocopherol reduces oxidative lipid damage and the number of TUNEL positive cells in the CA1 region of the hippocampus

skeleton

decreased osteoclast cell number ( J:80503 )

• reduced osteoclast numbers

short femur ( J:80503 )

osteopetrosis ( J:80503 )

• trabecular bone fraction in the metaphyseal region is increased about 3-fold compared to wild-type mice

growth/size/body

decreased body weight ( J:80503 )

postnatal growth retardation ( J:81240 )

• treatment of mice with the antioxidant alpha-tocopherol did not improve body weight gain

immune system

decreased B cell number ( J:80503 )

decreased osteoclast cell number ( J:80503 )

• reduced osteoclast numbers

limbs/digits/tail

short femur ( J:80503 )

hematopoietic system

decreased B cell number ( J:80503 )

decreased osteoclast cell number ( J:80503 )

• reduced osteoclast numbers

homeostasis/metabolism

decreased insulin secretion ( J:64878 )

• the pancreatic insulin content of 8 week old homozygotes is approximately 34 mg/g, much lower than the 171 mg/g in wildtype controls, but the glucagon content of the pancreas is normal

hypoglycemia ( J:64878 )

• in oral glucose tolerance tests homozygotes show hypoglycemia relative to wildtype controls at 0, 30, 60, and 120 minutes after glucose load, but post-fasting GH, TSH and ACTH levels are normal

decreased circulating insulin level ( J:64878 )

increased insulin sensitivity ( J:64878 )

• intraperitoneal insulin tolerance test using 0.05U/kg human insulin in 6 to 8 week old mice results in a rapid, sustained diminution in blood glucose from an already lower than normal starting point

• homozygotes have higher than normal expression of solute carrier family 2 member 4 in the skeletal muscle

endocrine/exocrine glands

decreased insulin secretion ( J:64878 )

• the pancreatic insulin content of 8 week old homozygotes is approximately 34 mg/g, much lower than the 171 mg/g in wildtype controls, but the glucagon content of the pancreas is normal