All Phenotypes Ccs<tm1Pcw> MGI Mouse

abnormal copper homeostasis ( J:80627 )

• metabolic labeling with 64Cu indicates that reduction of SOD1 activity is the direct result of impaired copper incorporation into SOD1

• no 64Cu-labeled SOD1 are detected in brain or spinal cord lysates from mutant mice, although low levels are detected in kidney or liver lysates

• however, no abnormalities are observed in Cu uptake, distribution, or incorporation into other cuproenzymes

abnormal enzyme/coenzyme activity ( J:80627 )

• although homozygotes have normal protein levels of soluble superoxide dismutase 1 (SOD1), they display significant reductions in SOD1 activity relative to wild-type mice

• all mutant tissues examined (including brain, spinal cord, muscle, lung, heart, and kidney) retain ~10-20% of normal SOD1 activity with the exception of liver, which retains ~30%

increased cellular sensitivity to oxidative stress ( J:80627 )

• homozygotes display increased sensitivity to paraquat toxicity, as shown by a marked edema and hemorrhage in the lungs and a listless behavior at 1 hr after exposure

• after i.p. injection of paraquat at 15 mg/kg body weight, ~60% of homozygotes die with an average survival time of 5 days

• after i.p. injection of paraquat at 25 mg/kg body weight, >90% of homozygotes die with an average survival time of 4 days, whereas ~90% wild-type mice remain unaffected

decreased corpora lutea number ( J:80627 )

• mutant ovaries contain fewer numbers of corpora lutea than wild-type ovaries

abnormal ovarian follicle morphology ( J:80627 )

• abnormally developed follicles are frequently observed in mutant ovaries

decreased mature ovarian follicle number ( J:80627 )

• mutant ovaries contain fewer numbers of mature follicles than wild-type ovaries

reduced female fertility ( J:80627 )

• over a 3 month mating period, female homozygotes produce only half the number of litters produced by heterozygous females (4 vs 8, respectively)

decreased litter size ( J:80627 )

• female homozygotes produce an average of 3.5 pups/litter vs 6.5 pups/litter in wild-type mice