Analysis Tools|
Allele Symbol Allele Name Allele ID |
Nr1h2tm1.1Gstr targeted mutation 1.1, Gertrud Schuster MGI:2653342 |
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| Summary |
5 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• lipid (cholesteryl esters) accumulation in sertoli cells
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• lipid (cholesteryl esters) accumulation in sertoli cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• when mice are fed a diet with 2% cholesterol, levels of 24- and 27-hydroxycholesterol are different from those in wild-type mice
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• at 16 months, but not at 6 months, of age, retinas show accumulation of beta-amyloid (Abeta) aggregates in and around retinal ganglion cells (RGCs); in contrast, Abeta deposits are much smaller and only occasionally found in wild-type retinas
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• mice exhibit scattered golden patches on the surface of the lung, indicating some lipid accumulation in the lungs
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• at 6 months of age, microglial cells in the optic nerve are ameboid in shape (i.e. activated); in contrast, only resting microglia are seen in the optic nerve of wild-type controls
• by 16 months of age, the number of active microglial cells in the optic nerve is significantly higher than that in wild-type controls
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• at 6 months of age, microglial cells in the optic nerve are ameboid in shape (i.e. activated); in contrast, only resting microglia are seen in the optic nerve of wild-type controls
• by 16 months of age, the number of active microglial cells in the optic nerve is significantly higher than that in wild-type controls
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• mice exhibit scattered golden patches on the surface of the lung, indicating some lipid accumulation in the lungs
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• at 6 months of age, the number of glutamine synthetase (GS)-positive (i.e. functional) oligodendrocytes in the optic nerve is lower than that in wild-type controls, indicating impaired oligodendrocyte maturation
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• at 16 months of age, the number of Oligo2-positive and GS-positive oligodendrocytes in the optic nerve is significantly lower than that in wild-type controls
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• at 6 months of age, microglial cells in the optic nerve are ameboid in shape (i.e. activated); in contrast, only resting microglia are seen in the optic nerve of wild-type controls
• by 16 months of age, the number of active microglial cells in the optic nerve is significantly higher than that in wild-type controls
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• at 16 months, but not at 6 months, of age, retinas show accumulation of beta-amyloid (Abeta) aggregates in and around retinal ganglion cells (RGCs); in contrast, Abeta deposits are much smaller and only occasionally found in wild-type retinas
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• at 16 months, but not at 6 months, of age, mice show accumulation of beta-amyloid (Abeta) aggregates in and around retinal ganglion cells (RGCs); in contrast, Abeta deposits are much smaller and only occasionally found in wild-type retinas
• at 6 and 16 months of age, the % of amyloid A4-positive RGCs is significantly higher than that in wild-type retinas
• however, no significant change in the level of apoptosis or autophagy is observed in RGCs
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• at 16 months, but not at 6 months, of age, the number of RGCs is significantly reduced relative to that in wild-type controls
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• at 6 months of age, the optic nerve shows a significant reduction in aquaporin 4 (AQP4) expression with no significant change in GFAP expression
• by 16 months of age, expression of both AQP4 and GFAP is markedly decreased, indicating loss of AQP4 in astrocytes in the optic nerve
• however, no AQP4 antibodies are detected in serum
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• as loss of AQP4 and microglial activation in the optic nerve precedes RGC loss and accumulation of Abeta aggregates in the retina, the cause of neuronal loss appears to be optic nerve degeneration
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• at 6 months of age, the number of glutamine synthetase (GS)-positive (i.e. functional) oligodendrocytes in the optic nerve is lower than that in wild-type controls, indicating impaired oligodendrocyte maturation
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• at 16 months of age, the number of Oligo2-positive and GS-positive oligodendrocytes in the optic nerve is significantly lower than that in wild-type controls
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• when mice are fed a diet with 2% cholesterol, levels of 24- and 27-hydroxycholesterol are different from those in wild-type mice
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• at 6 months of age, microglial cells in the optic nerve are ameboid in shape (i.e. activated); in contrast, only resting microglia are seen in the optic nerve of wild-type controls
• by 16 months of age, the number of active microglial cells in the optic nerve is significantly higher than that in wild-type controls
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• at 6 months of age, the optic nerve shows a significant reduction in aquaporin 4 (AQP4) expression with no significant change in GFAP expression
• by 16 months of age, expression of both AQP4 and GFAP is markedly decreased, indicating loss of AQP4 in astrocytes in the optic nerve
• however, no AQP4 antibodies are detected in serum
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• as loss of AQP4 and microglial activation in the optic nerve precedes RGC loss and accumulation of Abeta aggregates in the retina, the cause of neuronal loss appears to be optic nerve degeneration
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• mice show progressive loss of ganglion cells and accumulation of beta-amyloid (Abeta) in the retina
• however, no significant change in the activation of glial cells or in the expression of inflammatory mediators is observed in the retina
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• at 16 months, but not at 6 months, of age, mice show accumulation of beta-amyloid (Abeta) aggregates in and around retinal ganglion cells (RGCs); in contrast, Abeta deposits are much smaller and only occasionally found in wild-type retinas
• at 6 and 16 months of age, the % of amyloid A4-positive RGCs is significantly higher than that in wild-type retinas
• however, no significant change in the level of apoptosis or autophagy is observed in RGCs
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• at 16 months, but not at 6 months, of age, the number of RGCs is significantly reduced relative to that in wild-type controls
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• at 16 months, but not at 6 months, of age, the retinal nerve fiber layer is significantly reduced relative to that in wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no lipid accumulation in sertoli cells were observed
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
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• lipid (cholesteryl esters) accumulation in sertoli cells
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• lipid (cholesteryl esters) accumulation in sertoli cells
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by 1 year of age, oil red O staining indicates the presence of lipid-laden cells around the median eminence
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• mice begin to die after 12 months of age, with an overall survival of 16.5 +/- 2.9 months
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• mice exhibit multiple lesions with a high density of disorganized epithelial cells in the lungs at 14 months of age, with lesions present in the alveolar space and in the lung parenchyma
• marker analysis indicates that lesions are squamous cell lung carcinoma-like lesions involving p63, CK14, Sox2+ and TTF1 and pro-SPC-negative epithelial cells and not adenocarcinomas
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• by 1 year of age, oil red O staining shows accumulation of lipid droplets around abnormal microvessels in substantia nigra pars reticularis
• enlarged and distorted brain blood vessels are predominantly observed in the pars reticularis of the substantia nigra and globus pallidus; an increase in both number and size of brain vessels is revealed by H&E staining
• fewer microvessels are affected in the hippocampus and cerebellum, with only a few being abnormal in the cerebral cortex
• although microvessels show normal endothelial cells and tight junctions, pericytes contain lipofuscin, collagen bundles appear thick and disorganized, and astrocytic feet are swollen and contain pale lipid vacuoles and myelin-like inclusions
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• some double homozygotes show evidence of previous hemorrhage in the thalamus, globus pallidus, pontin, and hippocampus
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• as double homozygotes age, perivascular astrocytes accumulate lipid vacuoles and myelin-like or laminar-like structures
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• the neuronal deficit is accompanied by a significant increase in the number of astrocytes in the substantia nigra and globus pallidus
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• by 1 year of age, oil red O staining indicates the presence of lipid-laden cells around the median eminence
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• by 1 year of age, oil red O staining indicates the presence of lipid-laden cells around the lateral ventricle, third ventricle, and fourth ventricle
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• ependymal cells, esp. those around the third ventricle and cerebral aqueduct, contain large lipid vacuoles and appear swollen
• no visible space is observed between ependymal cells and choroid epithelial cells
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• by 1 year of age, the size of the fourth ventricle is decreased but the reduction is not as severe as that observed in the lateral and third ventricles
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• by 1 year of age, the lateral ventricles are closed and lined with lipid-laden cells
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• the size of lateral ventricles is significantly reduced with little empty space left relative to wild-type control mice
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• the cytoplasm of choroid plexus epithelial cells is filled with lipid vacuoles, and mitochondria are smaller than normal
• no visible space is observed between ependymal cells and choroid epithelial cells
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• no choroid plexus and no villi are detected; instead, a pale layer in the lateral ventricle, with an increased number of blood vessels, is observed
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• by 1 year of age, the third ventricle is closed due to accumulation of lipid droplets; only a thin split can be observed in some mutant mice
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• the dorsal third ventricle is also reduced in size, but the reduction is not as severe as that observed in the lateral and third ventricles
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• by 1 year of age, oil red O staining indicates the presence of lipid-laden cells around the cerebral aqueduct
• the size of the cerebral aqueduct is decreased but the reduction is not as severe as that observed in the lateral and third ventricles
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• aging double homozygotes display cholesterol clefts and foamy cells in the pars reticularis of substantia nigra, as revealed by toluidine blue staining
• a severe destruction by lipid crystal clefts is observed
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• thin uncompacted myelin sheaths without major dense lines are observed in substantia nigra pars reticularis
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• aging double homozygotes display a decreased number of neurons in the substantia nigra and globus pallidus relative to wild-type littermates
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• many dark-colored neurons are observed around the abnormal brain blood vessels, showing nuclear and cytoplasmic condensation with condensed and packed ribosomes and lipofuscin in the cytoplasm
• the Golgi apparatus is swollen or condensed, and plasma and nuclear membranes are ruffled, whereas mitochondria appear unaffected
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• by 1 year of age, the central canal of the spinal cord is reduced in size, but the reduction is not as severe as that observed in the lateral and third ventricles
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• global axon dysmyelination with thin uncompacted myelin sheaths without major dense lines is observed in substantia nigra pars reticularis
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• aging double homozygotes display lipid accumulation around the blood-CSF barrier, the blood-brain barrier, and specific brain regions including the lateral ventricle, third ventricle, cerebral aqueduct, fourth ventricle, median eminence subfornical organ, and organum vasculosum of the lamina terminalis, as well as the pars reticularis of substantia nigra, globus pallidus, and subthalamic nucleus
• in these regions, lipid-laden cells are observed primarily around the blood vessels
• a marked accumulation of ApoE protein is noted in substantia nigra and cells surrounding the lateral ventricle; ApoE-positive cells are also found around blood vessels in the cerebral cortex
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• expression of several target genes involved in cholesterol efflux from astrocytes is significantly reduced
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• mice show progressive lipid accumulation in the lungs, with focal spots along the margin of the lungs at 3 months, lesions that spread from the periphery toward the center at 7 months, and by 14 months, most of the lung is covered by a golden coat of lipid
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• 12 month old lungs show lymphoid hyperplasia around vessels and CD3+ inflammatory T cells infiltrating the parenchyma, and large clusters of CD206+ macrophages in alveolar spaces indicating chronic lung inflammation
• myeloperoxidase, a neutrophil marker, is highly expressed in lung macrophages and many cells express inflammatory cytokines IL1-beta and TNF-alpha
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• mice show progressive lipid accumulation in the lungs
• by 3 months of age, mice accumulate lipids in the distal parts of the lung close to the pleural surface and over the next 12 months, progressive and massive lipid deposition is seen in type 1 and 2 pneumocytes, in the alveolar wall, and in alveolar macrophages
• massive lipid accumulation is seen in the cells surrounding the hyperplastic epithelial lesions in 14 month old mice and in epithelial cells in the bronchioles
• lipid accumulation in lung is accompanied by loss of Cav-1+ type I pneumocytes, the proliferation and dysplasia of type 2 pneumocytes, and the appearance of pro-SPC negative cuboidal epithelial cells lining the alveoli
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• mice exhibit multiple lesions with a high density of disorganized epithelial cells in the lungs at 14 months of age, with lesions present in the alveolar space and in the lung parenchyma
• marker analysis indicates that lesions are squamous cell lung carcinoma-like lesions involving p63, CK14, Sox2+ and TTF1 and pro-SPC-negative epithelial cells and not adenocarcinomas
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• lung shows extensive remodeling of the alveolar regions
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• lipofibroblasts show increased size of lipid droplets around the nucleus
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• type 2 pneumocytes show abnormal lamellar bodies
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• severe dyspnea
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• by 1 year of age, oil red O staining shows accumulation of lipid droplets around abnormal microvessels in substantia nigra pars reticularis
• enlarged and distorted brain blood vessels are predominantly observed in the pars reticularis of the substantia nigra and globus pallidus; an increase in both number and size of brain vessels is revealed by H&E staining
• fewer microvessels are affected in the hippocampus and cerebellum, with only a few being abnormal in the cerebral cortex
• although microvessels show normal endothelial cells and tight junctions, pericytes contain lipofuscin, collagen bundles appear thick and disorganized, and astrocytic feet are swollen and contain pale lipid vacuoles and myelin-like inclusions
|
|
• some double homozygotes show evidence of previous hemorrhage in the thalamus, globus pallidus, pontin, and hippocampus
|
|
• aging double homozygotes contain foamy cells in the pars reticularis of substantia nigra, as revealed toluidine blue staining
(J:81790)
• foamy cells are filled with lipid remnants; only a few organelles are left
(J:81790)
• a few small lipid droplets of less intensity are also observed in the cerebral cortex, hippocampus, cerebellum, and spinal cord
(J:81790)
• mice show massive accumulation of foam cells in the lungs
(J:234268)
|
|
• aging double homozygotes contain foamy cells in the pars reticularis of substantia nigra, as revealed toluidine blue staining
(J:81790)
• foamy cells are filled with lipid remnants; only a few organelles are left
(J:81790)
• a few small lipid droplets of less intensity are also observed in the cerebral cortex, hippocampus, cerebellum, and spinal cord
(J:81790)
• mice show massive accumulation of foam cells in the lungs
(J:234268)
|
|
• 12 month old lungs show lymphoid hyperplasia around vessels and CD3+ inflammatory T cells infiltrating the parenchyma, and large clusters of CD206+ macrophages in alveolar spaces indicating chronic lung inflammation
• myeloperoxidase, a neutrophil marker, is highly expressed in lung macrophages and many cells express inflammatory cytokines IL1-beta and TNF-alpha
|
|
• aging double homozygotes contain foamy cells in the pars reticularis of substantia nigra, as revealed toluidine blue staining
(J:81790)
• foamy cells are filled with lipid remnants; only a few organelles are left
(J:81790)
• a few small lipid droplets of less intensity are also observed in the cerebral cortex, hippocampus, cerebellum, and spinal cord
(J:81790)
• mice show massive accumulation of foam cells in the lungs
(J:234268)
|
|
• as double homozygotes age, perivascular astrocytes accumulate lipid vacuoles and myelin-like or laminar-like structures
|
|
• the neuronal deficit is accompanied by a significant increase in the number of astrocytes in the substantia nigra and globus pallidus
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung squamous cell carcinoma | DOID:3907 | J:234268 | ||
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 09/30/2025 MGI 6.24 |
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