Phenotypes Associated with This Genotype

Genotype
MGI:4361574

• Allelic Composition: Mt1^tm1Bri/Mt1^tm1Bri; Mt2^tm1Bri/Mt2^tm1Bri
• Genetic Background: involves: 129S7/SvEvBrd

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

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:120459 )

• mice are more sensitive to acetaminophen-induced lethality compared with similarly treated wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:33276 )

N • mice exhibit normal copper levels

increased circulating alanine transaminase level ( J:120459 )

• in acetaminophen-treated mice

abnormal lipid homeostasis ( J:120459 )

• acetaminophen-induced lipid peroxidation is increased compared to in similarly treated wild-type mice

abnormal zinc homeostasis ( J:34407 )

• neonates exhibit a 60% decrease in hepatic zinc levels compared to in wild-type mice

• at 3 weeks, mice from dams fed a low zinc diet exhibit persistently low kidney and bone zinc levels

• however, kidney zinc levels in neonates are normal

• following administration of zinc, mice exhibit a 100% less zinc accumulation in the liver and pancreas compared with similarly treated wild-type mice

abnormal liver zinc level ( J:34407 )

• neonates exhibit a 60% decrease in hepatic zinc levels compared to in wild-type mice

• following administration of zinc, mice exhibit a 100% less zinc accumulation in liver compared with similarly treated wild-type mice

increased susceptibility to xenobiotic induced morbidity/mortality ( J:120459 )

• mice are more sensitive to acetaminophen-induced lethality compared with similarly treated wild-type mice

increased physiological sensitivity to xenobiotic ( J:120459 )

• mice exhibit increased susceptibility to acetaminophen-induced hepatotoxicity, alanine aminotransferase, hepatic necrosis, lipid peroxidation, and lethality compared with similarly treated wild-type mice

• acetaminophen-induced injuries are not ameliorated by pretreatment with zinc unlike in similarly treated wild-type mice

• hepatocytes are more sensitive to acetaminophen and NAPQI-induced oxidative stress compared with similarly treated wild-type cells

• however, acetaminophen metabolism is normal

impaired wound healing ( J:53929 )

• following brain freeze injury, tissue damage is greater than in wild-type mice with increased microglia/macrophage accumulation around the lesion, different temporal microglial response, increased astrocytosis, and increased apoptosis in the brain

• 10 to 20 days post brain freeze injury, mice develop hemorrhage unlike similarly treated wild-type mice

renal/urinary system

increased glomerular capsule space ( J:34407 )

• regardless of diet zinc content, Bowman's spaces are swollen unlike in wild-type mice

abnormal renal glomerulus morphology ( J:34407 )

• unlike in wild-type mice, glomeruli remain close to the kidney capsule in mature kidneys at 3 weeks

• mice fed a low zinc diet exhibit a persistence of the glomeruli remaining close to the kidney unlike in similarly treated wild-type mice

• however, mice fed a normal diet exhibit normal kidney morphology

liver/biliary system

abnormal liver zinc level ( J:34407 )

• neonates exhibit a 60% decrease in hepatic zinc levels compared to in wild-type mice

• following administration of zinc, mice exhibit a 100% less zinc accumulation in liver compared with similarly treated wild-type mice

abnormal hepatocyte morphology ( J:120459 )

• hepatocytes are more sensitive to acetaminophen and NAPQI-induced oxidative stress indicated by lactate dehydrogenase leakage compared with similarly treated wild-type cells

hepatic necrosis ( J:120459 )

• in acetaminophen-treated mice

endocrine/exocrine glands

abnormal pancreas morphology ( J:34407 )

• when administered zinc, 4 of 6 mice exhibit abnormal pancreas morphology with acinar cell necrosis and fibrosis compared to 1 of 6 wild-type mice

cellular

astrocytosis ( J:53929 , J:103102 )

• freeze-injury mice continue to exhibit reactive astrogliosis 20 days post lesion unlike similarly treated wild-type mice (J:53929)

• decreased in MOG-treated mice (J:103102)

abnormal microglial cell morphology ( J:53929 , J:103102 )

• following brain freeze injury, mice exhibit increased microglia/macrophage accumulation around the lesion compared with similarly treated wild-type mice (J:53929)

• MOG-treated mice exhibit amoeboid or round microglia/macrophages compared to bushy microglia observed in similarly treated wild-type mice (J:103102)

increased sensitivity to induced cell death ( J:33276 )

• cells from E11 embryos exhibit increased cell death when cultured with copper compared with similarly treated heterozygous cells

increased neuron apoptosis ( J:103102 )

• in MOG-treated mice

increased brain apoptosis ( J:53929 )

• 10 and 20 days following brain freeze injury, mice exhibit more apoptosis in the brain compared with similarly treated wild-type mice

abnormal microglial cell physiology ( J:53929 )

• microglial temporal response to brain freeze injury is different than in similarly treated wild-type mice

oxidative stress ( J:103102 )

• MOG-treated mice exhibit increased oxidative stress in microglia/macrophages and neurons compared with similarly treated wild-type mice

cardiovascular system

hemorrhage ( J:53929 )

• 10 to 20 days post brain freeze injury, mice develop hemorrhage unlike similarly treated wild-type mice

hematopoietic system

abnormal microglial cell morphology ( J:53929 , J:103102 )

• following brain freeze injury, mice exhibit increased microglia/macrophage accumulation around the lesion compared with similarly treated wild-type mice (J:53929)

• MOG-treated mice exhibit amoeboid or round microglia/macrophages compared to bushy microglia observed in similarly treated wild-type mice (J:103102)

abnormal microglial cell physiology ( J:53929 )

• microglial temporal response to brain freeze injury is different than in similarly treated wild-type mice

increased macrophage cell number ( J:53929 )

• following brain freeze injury, mice exhibit increased microglia/macrophage accumulation around the lesion compared with similarly treated wild-type mice

immune system

abnormal microglial cell morphology ( J:53929 , J:103102 )

• following brain freeze injury, mice exhibit increased microglia/macrophage accumulation around the lesion compared with similarly treated wild-type mice (J:53929)

• MOG-treated mice exhibit amoeboid or round microglia/macrophages compared to bushy microglia observed in similarly treated wild-type mice (J:103102)

abnormal microglial cell physiology ( J:53929 )

• microglial temporal response to brain freeze injury is different than in similarly treated wild-type mice

increased macrophage cell number ( J:53929 )

• following brain freeze injury, mice exhibit increased microglia/macrophage accumulation around the lesion compared with similarly treated wild-type mice

increased interleukin-1 beta secretion ( J:103102 )

• MOG-treated mice exhibit increased IL1b production in the brain stem compared with similarly treated wild-type mice

increased interleukin-6 secretion ( J:103102 )

• MOG-treated mice exhibit increased IL6 production in the brain stem compared with similarly treated wild-type mice

increased tumor necrosis factor secretion ( J:103102 )

• MOG-treated mice exhibit increased TNF-alpha production in the brain stem compared with similarly treated wild-type mice

increased susceptibility to experimental autoimmune encephalomyelitis ( J:103102 )

• MOG-treated mice exhibit increased incidence of experimental autoimmune encephalomyelitis, increased inflammatory infiltrate including amoeboid or round microglia/macrophages, and CD3+ T cells, decreased reactive astrogliosis, increased production of IL1beta, IL6 and TNF-alpha in the brain stem, increased oxidative stress, and increased neuron and astrocytic apoptosis compared with similarly treated wild-type mice

nervous system

astrocytosis ( J:53929 , J:103102 )

• freeze-injury mice continue to exhibit reactive astrogliosis 20 days post lesion unlike similarly treated wild-type mice (J:53929)

• decreased in MOG-treated mice (J:103102)

abnormal microglial cell morphology ( J:53929 , J:103102 )

• following brain freeze injury, mice exhibit increased microglia/macrophage accumulation around the lesion compared with similarly treated wild-type mice (J:53929)

• MOG-treated mice exhibit amoeboid or round microglia/macrophages compared to bushy microglia observed in similarly treated wild-type mice (J:103102)

increased neuron apoptosis ( J:103102 )

• in MOG-treated mice

increased brain apoptosis ( J:53929 )

• 10 and 20 days following brain freeze injury, mice exhibit more apoptosis in the brain compared with similarly treated wild-type mice

abnormal microglial cell physiology ( J:53929 )

• microglial temporal response to brain freeze injury is different than in similarly treated wild-type mice