Phenotypes associated with this allele

• Allele Symbol: Slc39a4^tm2Gka
• Allele Name: targeted mutation 2, Glen K Andrews
• Allele ID: MGI:5438020
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Slc39a4^tm2Gka/Slc39a4^tm2Gka Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5438021

Genotype
MGI:5438021

cn1

• Allelic Composition: Slc39a4^tm2Gka/Slc39a4^tm2Gka; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

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

Growth retardation of tamoxifen treated Slc39a4^tm2Gka/Slc39a4^tm2Gka Tg(Vil1-cre/ERT2)23Syr/0 mice

mortality/aging

lethality at weaning, complete penetrance ( J:187178 )

• mice treated with tamoxifen as neonates die within a week of weaning unless excess zinc is provided in the drinking water

premature death ( J:187178 )

• 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

weight loss ( J:187178 )

• 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

postnatal growth retardation ( J:187178 )

• 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

abnormal mineral homeostasis ( J:187178 )

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

decreased intestinal iron level ( J:187178 )

• about a 50% decrease in iron levels in the small intestine by 4 days after tamoxifen treatment

abnormal copper level ( J:187178 )

• decrease in copper levels in the pancreas by 4 days after tamoxifen treatment

decreased intestine copper level ( J:187178 )

• by 4 days after tamoxifen treatment

• largest loss of copper occurs in the small intestine

decreased liver copper level ( J:187178 )

• by 4 days after tamoxifen treatment

increased liver copper level ( J:187178 )

• by 8 days after tamoxifen treatment

increased liver iron level ( J:187178 )

• levels are about twice normal by 8 days after tamoxifen treatment

abnormal zinc homeostasis ( J:187178 )

• 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

abnormal small intestinal crypt cell proliferation ( J:187178 )

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

decreased intestinal iron level ( J:187178 )

• about a 50% decrease in iron levels in the small intestine by 4 days after tamoxifen treatment

abnormal small intestine crypts of Lieberkuhn morphology ( J:187178 )

• progressive and profound disorganization of the crypt architecture after tamoxifen treatment

• crypts become elongated 2 days after tamoxifen treatment

abnormal Paneth cell morphology ( J:187178 )

• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted

abnormal small intestinal villus morphology ( J:187178 )

• 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

liver/biliary system

abnormal liver morphology ( J:187178 )

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

decreased liver copper level ( J:187178 )

• by 4 days after tamoxifen treatment

increased liver copper level ( J:187178 )

• by 8 days after tamoxifen treatment

increased liver iron level ( J:187178 )

• levels are about twice normal by 8 days after tamoxifen treatment

muscle

decreased muscle weight ( J:187178 )

• 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

decreased bone mass ( J:187178 )

• 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

abnormal small intestinal crypt cell proliferation ( J:187178 )

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

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:187178 )

• progressive and profound disorganization of the crypt architecture after tamoxifen treatment

• crypts become elongated 2 days after tamoxifen treatment

abnormal Paneth cell morphology ( J:187178 )

• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrodermatitis enteropathica		DOID:0050605	OMIM:201100	J:187178