Mouse Genome Informatics
cn
    Slc39a4tm2Gka/Slc39a4tm2Gka
Tg(Vil-cre/ERT2)23Syr/0

involves: 129P2/OlaHsd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Growth retardation of tamoxifen treated Slc39a4tm2Gka/Slc39a4tm2Gka Tg(Vil-cre/ERT2)23Syr/0 mice

mortality/aging
• mice treated with tamoxifen as neonates die within a week of weaning unless excess zinc is provided in the drinking water
• mice treated with tamoxifen (3 injections) 5 days after weaning die unless provided with excess zinc in the drinking water
• removal of excess zinc in the drinking water results in precipitous weight loss and death in mice treated with tamoxifen as neonates or after weaning
• excess zinc must be provided by day 6 after tamoxifen treatment to prevent lethality
• mice treated with tamoxifen at 7 weeks of age die around 1 week after the treatment

growth/size/body
• rapid weight loss after weaning in mice treated with tamoxifen as neonates unless excess zinc is provided in the drinking water
• rapid weight loss is seen within a few days of tamoxifen treatment in mice treated with tamoxifen (3 injections) 5 days after weaning despite normal food consumption and much of this weight loss involves loss of muscle and bone
• mice given a single injection of tamoxifen after weaning slowly lose weight, about half recover and resume normal growth
• rapid weight loss is also seen when mice are treated with tamoxifen at 7 weeks of age
• mice treated with tamoxifen as neonates provided excess zinc in the drinking water at weaning still fail to gain much body weight following weaning

homeostasis/metabolism
• increase in manganese in the liver by 4 days after tamoxifen treatment with levels about twice normal by 8 days after treatment
• about a 50% decrease in copper levels in the small intestine by 4 days after tamoxifen treatment
• decrease in copper levels in the pancreas by 4 days after tamoxifen treatment
• by 4 days after tamoxifen treatment
• largest loss of copper occurs in the small intestine
• by 4 days after tamoxifen treatment
• by 8 days after tamoxifen treatment
• levels are about twice normal by 8 days after tamoxifen treatment
• decrease in zinc levels in the small intestine, pancreas and liver at 4 days after tamoxifen treatment
• decrease in zinc levels correlates with the beginning of weight loss
• levels in the liver normalize by 8 days after tamoxifen treatment

digestive/alimentary system
• decrease in proliferation at 2, 4 and 6 days after tamoxifen treatment
• progressive and profound disorganization of the villus after tamoxifen treatment
• by 6 days after tamoxifen treatment epithelial cells have lost much of their columnar morphology becoming cuboidal with centric nuclei
• by 6 days after tamoxifen treatment the lamina propria appears disorganized, occupies more space in the villi, and often contains red blood cells and cells with pyknotic nuclei
• progressive and profound disorganization of the crypt architecture after tamoxifen treatment
• crypts become elongated 2 days after tamoxifen treatment
• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted
• about a 50% decrease in copper levels in the small intestine by 4 days after tamoxifen treatment

liver/biliary system
• increase in manganese in the liver by 4 days after tamoxifen treatment with levels about twice normal by 8 days after treatment
• by 4 days after tamoxifen treatment
• by 8 days after tamoxifen treatment
• levels are about twice normal by 8 days after tamoxifen treatment

muscle
• rapid muscle weight loss is seen within a few days of tamoxifen treatment in mice treated with tamoxifen 5 days after weaning despite normal food consumption

skeleton
• loss of bone mass is seen within a few days of tamoxifen treatment in mice treated with tamoxifen 5 days after weaning despite normal food consumption

cellular
• decrease in proliferation at 2, 4 and 6 days after tamoxifen treatment

endocrine/exocrine glands
• progressive and profound disorganization of the crypt architecture after tamoxifen treatment
• crypts become elongated 2 days after tamoxifen treatment
• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted

Mouse Models of Human Disease
OMIM IDRef(s)
Acrodermatitis Enteropathica, Zinc-Deficiency Type; AEZ 201100 J:187178