Phenotypes for Grn MGI:6279297 MGI Mouse

abnormal body weight ( J:268827 )

• aged (12-15 months) female homozygotes are overweight but exhibit normal body weight at old age (>18 months)

• however, body weight is normal in both sexes at a young age (8-12 weeks)

enlarged kidney ( J:268827 )

• kidneys are significantly enlarged at 12-15 months of age

increased kidney weight ( J:268827 )

• kidney weight per body weight is significantly increased at 12-15 months of age

increased liver weight ( J:268827 )

• liver weight per body weight is significantly increased at 12-15 months of age

increased fluid intake ( J:268827 )

• aged homozygotes show a significantly increased 24h water consumption in Phenomaster cages and a nearly doubled 24h drinking volume in Metabolic Cages relative to wild-type controls

• however, drinking behavior is normal at a young age

polydipsia ( J:268827 )

• aged homozygotes exhibit polydipsia with significantly more daily water lickings in the IntelliCage during both free drinking and restricted drinking relative to wild-type controls

• at 12-15 months of age, polydipsia is noted during both tap water or sweetened water presentation, with daily drinking volumes of about 7 and 18 ml/d for tap and sweet water, respectively, relative to 3 and 10 ml/d in wild-type controls

• however, young homozygotes behave normally

increased food intake ( J:268827 )

• aged homozygotes show a significantly increased 24h food consumption in Phenomaster cages relative to wild-type controls

• at 12-15 months of age, tap water polydipsia is accompanied with overfeeding, whereas feeding drops to a minimum in both genotypes with sweetened water

• however, feeding behavior is normal at a young age

enlarged kidney ( J:268827 )

• kidneys are significantly enlarged at 12-15 months of age

increased kidney weight ( J:268827 )

• kidney weight per body weight is significantly increased at 12-15 months of age

decreased urine creatinine level ( J:268827 )

• urine creatinine concentrations are significantly decreased in aged homozygotes

decreased urine potassium level ( J:268827 )

• urine potassium concentrations are significantly decreased in aged homozygotes

decreased urine magnesium level ( J:268827 )

• urine magnesium concentrations are significantly decreased in aged homozygotes

decreased urine osmolality ( J:268827 )

• aged homozygotes show a significant decrease in urine osmolality relative to wild-type controls

• at 12-16 months of age, urine specific gravity is significantly decreased during both free drinking and restricted drinking, suggesting renal water loss

dilated kidney collecting duct ( J:268827 )

• aged kidneys exhibit reduced AQP2 expression in the inner medulla and widening of AQP2+ collecting ducts

dilated renal tubule ( J:268827 )

• aged kidneys show mildly widened tubules but no overt tubulopathy

abnormal kidney physiology ( J:268827 )

• aged homozygotes show increased vasopressin levels in the kidney

kidney inflammation ( J:268827 )

• aged kidneys show significantly higher numbers of F4/80+ macrophages within the interstitium and perivascular regions relative to wild-type kidneys

• however, no signs of glomerulonephritis, tubulonephritis or tubulosclerosis are observed

abnormal renal water homeostasis ( J:268827 )

• aged homozygotes exhibit renal water loss without glucosuria but with high vasopressin levels, suggesting nephrogenic diabetes insipidus

polyuria ( J:268827 )

• aged homozygotes exhibit a significant increase in 24h urine volume during both free drinking and restricted drinking relative to wild-type controls

• at 12-16 months of age, the 24h urine volume is significantly increased, as confirmed in Metabolic cages

• however, urine and plasma glucose concentrations are normal, excluding osmotic polyuria

homeostasis/metabolism phenotype ( J:268827 )

N

• aged homozygotes exhibit normal plasma C-reactive protein (CRP) levels, urine and plasma glucose concentrations, plasma creatinine and creatinine clearance, urea excretion, and urine albumin concentrations relative to wild-type controls

• no alterations in serum electrolytes or serum osmolality are observed in euhydrated aged homozygotes

decreased urine creatinine level ( J:268827 )

• urine creatinine concentrations are significantly decreased in aged homozygotes

abnormal circulating hormone level ( J:268827 )

• aged homozygotes show a significant decrease in plasma agouti-related protein (AgRP) levels relative to wild-type controls

increased circulating antidiuretic hormone level ( J:268827 )

• aged homozygotes show a ~3-fold increase in plasma vasopressin levels relative to wild-type controls

increased circulating ghrelin level ( J:268827 )

• aged homozygotes show a significant increase in plasma ghrelin levels relative to wild-type controls

decreased urine potassium level ( J:268827 )

• urine potassium concentrations are significantly decreased in aged homozygotes

abnormal zinc homeostasis ( J:268827 )

• plasma zinc levels are significantly decreased in aged homozygotes

decreased urine magnesium level ( J:268827 )

• urine magnesium concentrations are significantly decreased in aged homozygotes

decreased urine osmolality ( J:268827 )

• aged homozygotes show a significant decrease in urine osmolality relative to wild-type controls

• at 12-16 months of age, urine specific gravity is significantly decreased during both free drinking and restricted drinking, suggesting renal water loss

abnormal hypothalamus morphology ( J:268827 )

• aged brains exhibit hypothalamic astrogliosis

• hypothalamic vasopressin-positive neurons appear to be enlarged but reduced in numbers in aged brains

abnormal paraventricular hypothalamic nucleus morphology ( J:268827 )

• aged brains show stronger vasopressin immunofluorescence in the paraventricular hypothalamic nuclei

abnormal supraoptic nucleus morphology ( J:268827 )

• aged brains show stronger vasopressin immunofluorescence in the supraoptical hypothalamic nuclei

astrocytosis ( J:268827 )