Analysis Tools
cellular
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• of MEFs after 48 hours of culturing in normoxia or hypoxia conditions
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Allele Symbol Allele Name Allele ID |
Vhltm1Jae targeted mutation 1, Rudolf Jaenisch MGI:2136645 |
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| Summary |
24 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• of MEFs after 48 hours of culturing in normoxia or hypoxia conditions
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• pockets of inflammation
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• dilated lymphatic vessels
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• vascular ectasia
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• unilateral and bilateral macroscopic cysts that vary in number and size are seen in 3 of 10 mice
• multiple microscopic cysts are also seen with 3 of 10 having cysts of tubular origin and 7 of 10 having cysts of glomerular origin
• cysts of both tubular and glomerular origin may occur in the same mouse
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• cavernous hepatic hemangiomas seen in mice at 2 - 6 months of age and with increased frequency in mice older than 6 months
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• proliferation of endothelial cells in hepatic blood vessels
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• vascular ectasia
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• hepatic vascular angiectasia
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• cavernous hepatic hemangiomas seen in mice at 2 - 6 months of age and with increased frequency in mice older than 6 months
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• average red blood cell count is 10.77 x 106 compared to 9.3 x 106 in controls
• develop erythrocytosis as indicated by reddening of paws and muzzle
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• hemoglobin content is 19.38 g/dl compared to 13.24 g/dl in controls
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• pockets of inflammation
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• hepatic vascular angiectasia
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• unilateral and bilateral macroscopic cysts that vary in number and size are seen in 3 of 10 mice
• multiple microscopic cysts are also seen with 3 of 10 having cysts of tubular origin and 7 of 10 having cysts of glomerular origin
• cysts of both tubular and glomerular origin may occur in the same mouse
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:97652 , J:106705 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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N |
• no macroscopic or microscopic renal cysts are detected
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• moderate steatosis without angiectasia or endothelial cell proliferation is seen only in mutants over 9 months of age
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N |
• red cell count and hemoglobin levels are similar to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• severe steatosis
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• proliferation of endothelial cells in hepatic blood vessels
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• hepatic vascular angiectasia
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• hepatic vascular angiectasia
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:97652 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• livers appear histologically normal at 4 - 6 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• TPA-treated ears exhibit increased edema and inflammatory infiltration compared with similarly treated wild-type ears
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• pockets of inflammation
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• dilated lymphatic vessels
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• vascular ectasia
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• unilateral and bilateral macroscopic cysts that vary in number and size are seen in 4 of 22 mice
• multiple microscopic cysts are also seen with 5 of 20 having cysts of tubular origin and 7 of 20 having cysts of glomerular origin
• cysts of both tubular and glomerular origin may occur in the same mouse
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• cavernous hepatic hemangiomas seen in mice at 2 - 6 months of age and with increased frequency in mice older than 6 months
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• proliferation of endothelial cells in hepatic blood vessels
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• vascular ectasia
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• hepatic vascular angiectasia
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• cavernous hepatic hemangiomas seen in mice at 2 - 6 months of age and with increased frequency in mice older than 6 months
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• average red blood cell count is 11.7 x 106 compared to 9.3 x 106 in controls
• develop erythrocytosis as indicated by reddening of paws and muzzle
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• hemoglobin content is 20.05 g/dl compared to 13.24 g/dl in controls
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• pockets of inflammation
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• hepatic vascular angiectasia
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• unilateral and bilateral macroscopic cysts that vary in number and size are seen in 4 of 22 mice
• multiple microscopic cysts are also seen with 5 of 20 having cysts of tubular origin and 7 of 20 having cysts of glomerular origin
• cysts of both tubular and glomerular origin may occur in the same mouse
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:97652 , J:106705 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal frequencies of KLS cells (hematopoietic stem cells and multipotential progenitors) numbers of red blood cells and lymphocytes and hematocrit
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• early vertical branching from primary vascular plexuses in the retina
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• early vertical branching from primary vascular plexuses in the retina
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal hematocrit
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Vascular tumors in Vhltm1.1Jae/Vhl+ livers and vascular lesions in Vhltm1Jae/Vhltm1Jae Speer6-ps1Tg(Alb-cre)21Mgn/0 mice
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• die between 6 and 13 weeks of age
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• body weight is about 50% of wild-type
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• severe
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• numerous blood filled vascular cavities, but no large cavernous hemangiomas, are seen
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• severe
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• accumulation of neutral fats in hepatocytes is detectable by 2 weeks of age
(J:67505)
• severe steatosis
(J:97652)
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• foci of increased vascularization are present in the liver
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• proliferation of endothelial cells in hepatic blood vessels
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• hepatic vascular angiectasia
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• hepatic vascular angiectasia
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:67505 , J:97652 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hydronephrosis, characterized by an expansion of the renal pelvis
• however, mutants do not display histological abnormalities in the urothelium of the renal pelvis or ureter, or in the structure of the tubules in the kidney cortex or medulla
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex
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• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla
• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age
• cysts arise in collecting ducts and distal tubules
• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with
occasional papillary projections (atypical cysts)
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
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• mutants develop multiple epithelial tubule cysts in the kidney cortex
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• mutants develop multiple epithelial tubule cysts in the kidney medulla
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• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts
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• 3 of 14 mice show isolated regions of benign squamous metaplasia within the kidney cortex
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• kidney epithelial cells fail to maintain their primary cilia, resulting in uncontrolled proliferation and cyst formation
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• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
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• hyperproliferation of the urothelium in the renal pelvis is more pronounced than in single Pten mutants
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• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
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• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex
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| N |
• no tumors areas seen at 3-6 months of age, when mice are euthanized to avoid renal failure
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• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla
• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age
• cysts arise in collecting ducts and distal tubules
• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with
occasional papillary projections (atypical cysts)
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
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• mutants develop multiple epithelial tubule cysts in the kidney cortex
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• mutants develop multiple epithelial tubule cysts in the kidney medulla
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• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:137073 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exposed to hypoxic conditions exhibit reduced impairment in intestinal barrier function compared with similarly treated wild-type mice
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• TNBS-treated mice do not exhibit weight loss, as severe reduction in colon length, as much mortality, or an increase in intestinal permeability unlike similarly treated wild-type mice
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• TNBS-treated mice do not exhibit weight loss, as severe reduction in colon length, as much mortality, or an increase in intestinal permeability unlike similarly treated wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die at 6 to 8 weeks of age
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• at 6 weeks, the liver is friable and stippled with irregular yellow spots on a reddish black background unlike in wild-type mice
• hepatic vascularity is increased compared to in wild-type mice
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• at 6 weeks of age
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• livers contain irregular, dilated, blood filled sinusoids and cytoplasmic vacuolizations within hepatocytes with eccentric nuclei unlike in wild-type mice
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• in a mixed micro- and macrovesicular steatotic pattern
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• hepatic vascularity is increased compared to in wild-type mice
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• mice are runted
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• at 6 weeks of age
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• of paws and unfurred skin by 4 to 6 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• premature death beginning at ~6 months of age in mice with the highest levels of albuminuria (>1000 ug/ml)
• however, nonproteinuric mice survive to >1 year of age without overt health problems
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| N |
• at P5, all mice exhibit normal comma and S-shaped nephric figures as well as normal capillary loop stage and maturing stage glomeruli relative to wild-type controls
• no changes in peritubular microvessels or larger arterioles and veins are observed
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• dilated glomerular capillary lumen noted in mice with severe albuminuria as early as 4 weeks of age
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• mesangial hypercellularity noted in mice with severe albuminuria at 4 weeks of age
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• at 4 weeks of age, mice exhibit varying levels of albuminuria ranging from no detectable albumin to >1000 ug/ml in severe cases
• 54% of mice (males and females) are nonproteinuric with albumin levels ranging from 2.9 to 29.7 ug/ml, similar to those in wild-type controls
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• dilated medullary collecting ducts noted in nonproteinuric mice at 4 weeks of age
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• podocyte foot process broadening noted in all nonproteinuric mice at 4 weeks of age
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• significant decrease in podocyte number noted in both proteinuric and nonproteinuric mice at 4 weeks of age, as shown WT1 staining
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• incompletely fused or fragmented GBM noted on the subendothelial side of the capillary loop in nonproteinuric mice at 4 weeks of age
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• abnormal GBM thickenings with numerous subepithelial "humps" and subendothelial matrix projections noted in nonproteinuric mice at 4 weeks of age
• at 16 weeks of age, overall GBM thickness in nonproteinuric mice increases to ~100 nm more than in wild-type controls
• ectopic deposition of collagen alpha1alpha2alpha1(IV) noted in GBM humps beneath podocytes
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• mesangial matrix expansion noted in mice with severe albuminuria at 4 weeks of age
• slightly increased mesangial matrix noted in nonproteinuric mice at 4 weeks of age
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• glomerular crescents noted in mice with severe albuminuria at 4 weeks of age
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• severely fibrotic glomeruli noted in mice with massive albuminuria at 25 weeks of age
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• noted in mice with severe albuminuria at 25 weeks of age
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• dilated tubules containing proteinaceous casts and cellular debris noted in mice with severe albuminuria at 25 weeks of age
• occasional dilated tubules in nonproteinuric mice at 4 weeks of age
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• proteinaceous casts detected in dilated tubules of mice with severe albuminuria at 25 weeks of age
• proteinaceous casts also noted in dilated medullary collecting ducts of nonproteinuric mice at 4 weeks of age
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• end-stage renal failure observed in mice with the highest levels of albuminuria
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• at 33-41-weeks of age, increased BUN levels are noted in association with only the highest levels of albuminuria (>1000 ug/ml)
• severely nephrotic mice show a 6-fold increase in BUN levels relative to mice with lower levels of albuminuria
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• at 4 weeks of age, mice exhibit varying levels of albuminuria ranging from no detectable albumin to >1000 ug/ml in severe cases
• 54% of mice (males and females) are nonproteinuric with albumin levels ranging from 2.9 to 29.7 ug/ml, similar to those in wild-type controls
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• dilated glomerular capillary lumen noted in mice with severe albuminuria as early as 4 weeks of age
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• mesangial hypercellularity noted in mice with severe albuminuria at 4 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at weaning mice are runted
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• the number of dilated dermal blood vessels is increased compared to in wild-type mice
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• following application of an inflammatory stimuli
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• keratinocyte proliferation is increased
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• at P5
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• keratinocyte proliferation is increased
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 3-fold increase in the frequency of KLS cells (hematopoietic stem cells and multipotential progenitors)
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• 1.4-fold in the bone marrow
• 4-fold in the spleen
• increased mature erythroid (CFU-E) compared with immature erythroid (BFU-E)
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• severe by 2 months
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• 2.5-fold in the metaphyseal region
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• increased trabecular osteoblasts
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• in the metaphyseal and diaphyseal regions
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• hypervasculatization of the bone
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• red paw
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mean survival is 9 weeks
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• die between P16 and P18 due to sudden cardiac death
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• at 5 weeks and severe at 8 weeks
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• at 8 weeks, mice exhibit reduced left ventricular wall thickness and increased left ventricular end-diastolic dimension compared with control mice
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• at 5 weeks and severe at 8 weeks
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• neonates exhibit decreased heart rate at 10 days after birth
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• neonates exhibit frequent cardiac arrhythmia, consistent with sudden cardiac death
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• neonates exhibit increased QRS at 10 days after birth
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• exhibit increased QTc (c denotes correction for heart rate) and QTc dispersion at 10 days after birth
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• severe at 8 weeks of age
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• at 5 weeks and severe at 8 weeks
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• severe at 8 weeks of age
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• myocytes exhibit mitochondrial loss
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• at 5 weeks and severe at 8 weeks
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| sudden infant death syndrome | DOID:9007 |
OMIM:272120 |
J:193425 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• aberrant presence of dilated blood capillaries surrounding epididymal tubules indicating increased vascularization
• however, the genital tracts of males and females look normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tumors contain regions of cystadenoma characterized by adenoid structures identical to human cystadenoma lesions arising in epididymides
• cystadenoma display clear cell morphology
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• cysts and squamous epithelial hyperplasia in the oviduct
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• females exhibit hyperplasia and full squamous differentiation of the uterine endometrial lumen, endometrial hyperplasia, and endometrial hyperplasia with cyst formation
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• cysts and squamous epithelial hyperplasia in the cervix
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• squamous metaplasia is seen in the epididymis
• vascularization is increased in the epididymides
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• regions of squamous differentiation intermingle with the regions of cystadenoma
• cystadenomas appear to result from basal cell proliferation without differentiation, whereas regions of squamous metaplasia contain abundant basal cells in basal layers as well as cells with markers of epidermal differentiation
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• all mutants develop benign mixed adenosquamous genital tract tumors (in epididymis, vesicular glands, vas deferens, endometrium, and oviduct) resembling clear cell cystadenomas that form in patients with Von Hippel-Lindau syndrome (VHL)
• tumors arise simultaneously in all genital tract epithelia and show expansion of basal cells
• endometrial hyperplasia with cyst formation resembles cystadenoma and cystic lesions seen in broad ligament of females with VHL
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• tumors contain regions of cystadenoma characterized by adenoid structures identical to human cystadenoma lesions arising in epididymides
• cystadenoma display clear cell morphology
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:137442 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• proliferation of MEFs after 48 hours of culturing in normoxia or hypoxia conditions is normal
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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 04/30/2024 MGI 6.23 |
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