Phenotypes associated with this allele

• Allele Symbol: Grn^tm1.1Aidi
• Allele Name: targeted mutation 1.1, Aihao Ding
• Allele ID: MGI:4421705
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Grn^tm1.1Aidi/Grn^tm1.1Aidi	involves: C57BL/6 * C57BL/6J	MGI:4421707
hm2	Grn^tm1.1Aidi/Grn^tm1.1Aidi	involves: C57BL/6J	MGI:6279297

Genotype
MGI:4421707

hm1

• Allelic Composition: Grn^tm1.1Aidi/Grn^tm1.1Aidi
• Genetic Background: involves: C57BL/6 * C57BL/6J

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

Exaggerated tissue inflammation in Grn^tm1.1Aidi/Grn^tm1.1Aidi mice after infection with L. monocytogenes

immune system

microgliosis ( J:156824 )

• mice exhibit increased age-dependent microgliosis compared with wild-type mice

abnormal macrophage physiology ( J:156824 )

• activated bone marrow-derived macrophages exhibit increased killing potential compared with wild-type cells

• bone marrow-derived macrophages stimulated with Toll-like receptor agonist produce more MCP-1, CXCL1, IL6, IL12p40, and TNF compared with similarly treated wild-type cells

abnormal microglial cell physiology ( J:156824 )

• GM-CSF and LPS/IFN-gamma treated mice exhibit increased cytotoxicity compared with similarly treated wild-type mice

abnormal chemokine secretion ( J:156824 )

• bone marrow-derived macrophages stimulated with Toll-like receptor agonist produce more MCP-1 and CXCL1 compared with similarly treated wild-type cells

increased interleukin-12 secretion ( J:156824 )

• IL12p40 production is increased in bone marrow-derived macrophages stimulated with Toll-like receptor agonist compared to in similarly treated wild-type cells

increased interleukin-6 secretion ( J:156824 )

• in bone marrow-derived macrophages stimulated with Toll-like receptor agonist

increased tumor necrosis factor secretion ( J:156824 )

• in bone marrow-derived macrophages stimulated with Toll-like receptor agonist

increased susceptibility to bacterial infection ( J:156824 )

• following infection with Listeria monocytogenes, mice exhibit fewer monocytes in the spleen and higher Listeria burden in the spleen, liver, and brain compared to in wild-type mice

nervous system

microgliosis ( J:156824 )

• mice exhibit increased age-dependent microgliosis compared with wild-type mice

abnormal microglial cell physiology ( J:156824 )

• GM-CSF and LPS/IFN-gamma treated mice exhibit increased cytotoxicity compared with similarly treated wild-type mice

astrocytosis ( J:156824 )

• mice exhibit increased age-dependent astrocytosis compared with wild-type mice

homeostasis/metabolism

increased susceptibility to injury ( J:156824 )

• hippocampal slices starved of glucose and oxygen exhibit increased cell death compared with similarly treated wild-type slices

hematopoietic system

microgliosis ( J:156824 )

• mice exhibit increased age-dependent microgliosis compared with wild-type mice

abnormal macrophage physiology ( J:156824 )

• bone marrow-derived macrophages stimulated with Toll-like receptor agonist produce more MCP-1, CXCL1, IL6, IL12p40, and TNF compared with similarly treated wild-type cells

• activated bone marrow-derived macrophages exhibit increased killing potential compared with wild-type cells

abnormal microglial cell physiology ( J:156824 )

• GM-CSF and LPS/IFN-gamma treated mice exhibit increased cytotoxicity compared with similarly treated wild-type mice

Genotype
MGI:6279297

hm2

• Allelic Composition: Grn^tm1.1Aidi/Grn^tm1.1Aidi
• Genetic Background: involves: C57BL/6J

growth/size/body

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

behavior/neurological

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

renal/urinary system

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

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

N • 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

nervous system

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 )

• aged brains exhibit hypothalamic astrogliosis

abnormal hypothalamus secretion ( J:268827 )

• aged brains show increased vasopressin levels in the hypothalamus, in spite of astrogliosis

immune system

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

liver/biliary system

increased liver weight ( J:268827 )

• 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		J:268827