Phenotypes Associated with This Genotype

Genotype
MGI:6159332

• Allelic Composition: Slc30a10^tm1.1Sommu/Slc30a10^tm1.1Sommu
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA

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

Decreased body size of Slc30a10^tm1.1Sommu/Slc30a10^tm1.1Sommu mice

mortality/aging

premature death ( J:243657 )

• homozygotes are born at normal Mendelian ratios but start dying by ~6-8 weeks of age

• male homozygotes appear to die earlier than female homozygotes

growth/size/body

decreased body size ( J:243657 )

• although homozygotes are morphologically normal until P16-P18, they are significantly smaller in size than littermate controls after weaning

decreased body weight ( J:243657 )

• by 4 weeks of age, the weights of male and female homozygotes are ~40% and ~60% of littermate controls, respectively

• weight difference is greater and evident earlier in male than in female homozygotes

• when homozygotes are fed a low-manganese diet, body weights are comparable with those in controls at the 6-week time point

slow postnatal weight gain ( J:243657 )

• after ~P18, body weights of homozygotes fail to keep up with those of littermate controls

• failure to gain weight is exacerbated after weaning

homeostasis/metabolism

decreased circulating prolactin level ( J:243657 )

• at 6 weeks of age, serum prolactin levels are modestly reduced relative to those in littermate controls

• however, serum growth hormone, follicle-stimulating hormone, and adrenocorticotrophic hormone are normal, suggesting that anterior pituitary function is largely unaffected

increased circulating thyroid-stimulating hormone level ( J:243657 )

• at 6 weeks of age, serum levels of thyroid-stimulating hormone (TSH) are massively higher (~800-1,000-fold) than those in littermate controls

• male homozygotes exhibit higher serum TSH levels than female homozygotes

• when homozygotes are fed a low-manganese diet, TSH levels are comparable with those in controls at the 6-week time point

decreased circulating thyroxine level ( J:243657 )

• at 6 weeks of age, serum thyroxine levels are markedly lower (~50-80%) than those in littermate controls

• male homozygotes exhibit lower serum thyroxine levels than female homozygotes

• no differences in serum thyroxine levels are noted at P18

• when homozygotes are fed a low-manganese diet, thyroxine levels are comparable with those in controls at the 6-week time point

increased circulating copper level ( J:243657 )

• minor increase in blood copper at 6 weeks of age

increased circulating iron level ( J:243657 )

• minor increase in blood iron at 6 weeks of age

decreased liver glycogen level ( J:243657 )

• at 6 weeks of age, homozygotes exhibit no diffuse glycogen vacuolation in hepatocytes, suggesting that glycogen levels are depleted, unlike in littermate controls

increased brain iron level ( J:243657 )

• minor increase in brain iron at 6 weeks of age

abnormal manganese level ( J:243657 )

• at 6 weeks of age, manganese levels in the brain, blood, and liver are significantly (~20-60-fold) higher than those in littermate controls whereas zinc levels in the brain, blood, and liver remain normal

• at 1 month of age, thyroid manganese levels are 10-fold higher than in controls, whereas thyroid zinc, copper, and iron are not enhanced

• notably, at 1 month of age, the magnitude of increase in thyroid manganese levels (~10-fold) is significantly greater than that in the pituitary (only ~2-fold) but significantly lesser than the ~20-fold increase observed in the brain

increased circulating manganese level ( J:243657 )

• at 6 weeks of age, manganese levels in the blood are significantly higher than those in littermate controls

• at P18, blood manganese levels are already ~10-fold greater than those in controls

• a low-manganese diet only minimally reduces blood manganese in female homozygotes and has no effect in males

increased brain manganese level ( J:243657 )

• at 6 weeks of age, manganese levels in the brain are significantly higher than those in littermate controls

• when homozygotes are fed a low-manganese diet, manganese levels in the brain are significantly lower than those of homozygotes fed regular rodent chow

increased liver manganese level ( J:243657 )

• at 6 weeks of age, manganese levels in the liver are significantly higher than those in littermate controls

• when homozygotes are fed a low-manganese diet, manganese levels in the liver are significantly lower than those of homozygotes fed regular rodent chow

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:243657 )

• at 6 weeks of age, the thyroid gland shows extensive morphological alterations

abnormal thyroid follicle morphology ( J:243657 )

• at 6 weeks of age, the amount of colloid within the thyroid follicles is reduced

abnormal thyroid follicular cell morphology ( J:243657 )

• at 6 weeks of age, the thyroid follicular epithelial cells are hypertrophic

decreased activity of thyroid gland ( J:243657 )

• homozygotes develop hypothyroidism by 6 weeks of age, with male homozygotes more severely affected than female homozygotes

• a low-manganese diet produces lower tissue manganese levels and rescues the hypothyroidism phenotype

liver/biliary system

decreased liver glycogen level ( J:243657 )

• at 6 weeks of age, homozygotes exhibit no diffuse glycogen vacuolation in hepatocytes, suggesting that glycogen levels are depleted, unlike in littermate controls

increased liver manganese level ( J:243657 )

• at 6 weeks of age, manganese levels in the liver are significantly higher than those in littermate controls

• when homozygotes are fed a low-manganese diet, manganese levels in the liver are significantly lower than those of homozygotes fed regular rodent chow

abnormal hepatocyte morphology ( J:243657 )

• at 6 weeks of age, no diffuse glycogen vacuolation is observed in hepatocytes, unlike in littermate controls

• hepatocellular vacuolation is centered on centrilobular areas, suggesting a mild degenerative change

liver degeneration ( J:243657 )

• only mild degenerative changes are observed in liver at 6 weeks of age

nervous system

nervous system phenotype ( J:243657 )

N • surprisingly, brain histology is largely unaffected with no detectable tissue damage

increased brain iron level ( J:243657 )

• minor increase in brain iron at 6 weeks of age

increased brain manganese level ( J:243657 )

• at 6 weeks of age, manganese levels in the brain are significantly higher than those in littermate controls

• when homozygotes are fed a low-manganese diet, manganese levels in the brain are significantly lower than those of homozygotes fed regular rodent chow