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Phenotypes Associated with This Genotype
Genotype
MGI:6279297
Allelic
Composition
Grntm1.1Aidi/Grntm1.1Aidi
Genetic
Background
involves: C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Grntm1.1Aidi mutation (1 available); any Grn mutation (31 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• 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)

behavior/neurological
• 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
• 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
• 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

renal/urinary system
• urine creatinine concentrations are significantly decreased in aged homozygotes
• urine potassium concentrations are significantly decreased in aged homozygotes
• urine magnesium concentrations are significantly decreased in aged homozygotes
• 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
• aged kidneys exhibit reduced AQP2 expression in the inner medulla and widening of AQP2+ collecting ducts
• kidneys are significantly enlarged at 12-15 months of age
• kidney weight per body weight is significantly increased at 12-15 months of age
• aged kidneys show mildly widened tubules but no overt tubulopathy
• aged homozygotes show increased vasopressin levels in the kidney
• 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
• aged homozygotes exhibit renal water loss without glucosuria but with high vasopressin levels, suggesting nephrogenic diabetes insipidus
• 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
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
• urine creatinine concentrations are significantly decreased in aged homozygotes
• aged homozygotes show a significant decrease in plasma agouti-related protein (AgRP) levels relative to wild-type controls
• aged homozygotes show a ~3-fold increase in plasma vasopressin levels relative to wild-type controls
• aged homozygotes show a significant increase in plasma ghrelin levels relative to wild-type controls
• urine potassium concentrations are significantly decreased in aged homozygotes
• plasma zinc levels are significantly decreased in aged homozygotes
• urine magnesium concentrations are significantly decreased in aged homozygotes
• 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

nervous system
• aged brains exhibit hypothalamic astrogliosis
• hypothalamic vasopressin-positive neurons appear to be enlarged but reduced in numbers in aged brains
• aged brains show stronger vasopressin immunofluorescence in the paraventricular hypothalamic nuclei
• aged brains show stronger vasopressin immunofluorescence in the supraoptical hypothalamic nuclei
• aged brains exhibit hypothalamic astrogliosis
• aged brains show increased vasopressin levels in the hypothalamus, in spite of astrogliosis

immune system
• 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

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

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
nephrogenic diabetes insipidus DOID:12387 OMIM:125800
OMIM:304800
J:268827


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
08/13/2019
MGI 6.14
The Jackson Laboratory