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Allele Symbol Allele Name Allele ID |
Slc33a1tm1.1Lpu targeted mutation 1.1, Luigi Puglielli MGI:5634280 |
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| Summary |
2 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in most cases, embryonic growth arrest occurs at E8-E8.5
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• homozygotes exhibit severe retardation early in their development
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• homozygotes exhibit severe retardation early in their development
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• when housed in an open facility, heterozygotes display a reduced survival rate
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| N |
• when housed in a SPF facility, heterozygotes display no infection or tissue inflammation; no differences in major components of the innate or adaptive immune system are observed
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• when housed in an open facility, heterozygotes show increased numbers of splenic Ly6G+ neutrophils relative to wild-type controls
• however, no difference in the frequency of neutrophils is observed in the bone marrow
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• when housed in an open facility, heterozygotes show a decreased B-cell frequency in the blood
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• when housed in an open facility, heterozygotes show an increased frequency of B cells in peripheral nodes
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• heterozygotes exhibit activated microglia in the spinal cord and dentate gyrus
• PET imaging showed widespread microglia activation in the brain
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• when housed in an open facility, heterozygotes show a higher expression of the T-cell activation marker LFA-1 on T cells from pooled lymph nodes, indicating an ongoing immune response
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• when housed in an open facility, heterozygotes show increased plasma concentrations of several chemokines and cytokines, including IL-7, IL-18, CXCL6, CCL9 (MIP-3beta), and CCL19 (MIP-1gamma)
• in contrast, serum levels of CCL22, which is chemotactic for dendritic cells, monocytes, and chronically activated T cells, are significantly reduced
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• upon ex vivo T-cell receptor stimulation, T cells produce higher levels of inflammatory cytokines, including IL-17, IFN-gamma, and IL-4
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• upon ex vivo T-cell receptor stimulation, in heterozygotes housed in an open facility
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• upon ex vivo T-cell receptor stimulation, in heterozygotes housed in an open facility
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• upon ex vivo T-cell receptor stimulation, in heterozygotes housed in an open facility
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• at death, heterozygotes housed in an open facility, show moderate to severe inflammatory infiltration in several organs/tissues
• histology revealed neutrophils, mononuclear leukocytes, and multinucleate giant cells intermixed with morphologically abnormal cells
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• inflammation of the stomach mucosa
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• inflammation of the prostate parenchyma
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• inflammation of the preputial gland
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• PET imaging showed widespread inflammation in the brain
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• when housed in an open facility, adult heterozygotes exhibit severe conjunctivitis
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• inflammation of the bladder mucosa
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• when housed in an open facility, adult heterozygotes exhibit severe ulcerative dermatitis
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• when housed in an open facility, heterozygotes develop signs of active infections, such as severe conjunctivitis, dermatitis, and disseminated abscesses that test positive for common pathogens
• upon infection, heterozygotes are prone to an IL-17 neutrophil-dominated response causing the observed pathologies
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• PET imaging showed widespread inflammation in the brain
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• heterozygotes exhibit a lower FA (an index of fiber coherence) in the corpus callosum relative to wild-type controls
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• heterozygotes exhibit reduced thickness of the corpus callosum
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• heterozygotes exhibit activated microglia in the spinal cord and dentate gyrus
• PET imaging showed widespread microglia activation in the brain
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• heterozygotes exhibit reactive astrocytes in the spinal cord
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• heterozygotes display several features of axonal degeneration and myelinopathy in the white matter of the spinal cord
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• heterozygotes develop a neurodegenerative disease that affects the PNS and the CNS
• the neuronal phenotype is observed with mice housed in both SPF and open facilities, and is thus independent of the presence of pathogens in the environment
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• heterozygotes exhibit neuronal loss in both the dorsal and ventral horns of the spinal cord; lumbar sections are more affected
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• heterozygotes exhibit loss of axonal fibers in the sciatic nerve and axonal degeneration in the lumbar sections of the spinal cord
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• heterozygotes exhibit myelin degeneration in the sciatic nerve; degenerating features include onion bulbs with degenerating and regenerating myelin, and myelin outfolds
• myelinopathy is observed in the white matter of the spinal cord; degenerating features include vacuolar myelinopathy, myelin outfolds, and degenerating and regenerating myelin
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| N |
• when housed in a SPF facility, heterozygotes display no propensity to cancer and have a normal lifespan
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• when housed in an open facility, heterozygotes show increased propensity to malignancies that are either the direct cause of death/euthanasia or discovered upon necropsy
• malignancies include sarcoma, lymphoma, carcinoma, and carcinomatosis
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• focal pulmonary adenoma
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• spindle cell sarcoma of the spine and the pleura
• sarcoma invading the bone structure of the knee
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• when housed in an open facility, heterozygotes show increased numbers of splenic Ly6G+ neutrophils relative to wild-type controls
• however, no difference in the frequency of neutrophils is observed in the bone marrow
|
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• when housed in an open facility, heterozygotes show a decreased B-cell frequency in the blood
|
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• when housed in an open facility, heterozygotes show an increased frequency of B cells in peripheral nodes
|
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• heterozygotes exhibit activated microglia in the spinal cord and dentate gyrus
• PET imaging showed widespread microglia activation in the brain
|
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• when housed in an open facility, heterozygotes show a higher expression of the T-cell activation marker LFA-1 on T cells from pooled lymph nodes, indicating an ongoing immune response
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• at 10-12 months of age, heterozygotes develop impaired motor functions
• however, no PNS or CNS anomalies are detected at birth and muscle histology appears normal
• no widespread motor function deficits are observed, as determined by open-field or rotarod tests
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• at 10-12 months of age, heterozygotes display intermittent hind-leg clasping and abnormal body rotation, as assessed by the hind-leg clasping reflex
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• at 10-12 months of age, heterozygotes display reduced grip strength on the inverted cage lid
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• at 10-12 months of age, heterozygotes show increased latency to pain response in the hot plate test
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• heterozygotes display abnormal activation of autophagy
• EM of spinal cord neurons revealed large autophagosomes and autolysosomes and other features consistent with excessive or aberrant induction of autophagy; similar features are noted in brain and in isolated neurons
• LC3beta-positive neurons are detected in the spinal cord, indicating ongoing autophagy, unlike in wild-type controls
• heterozygous mutant MEFs show enlarged ER and aberrant autophagic structures, increased levels of autophagy markers, and decreased levels of the autophagy cargo protein p62; the autophagy phenotype can be rescued after expression of a dominant gain-of-acetylation mutant form of the ER-associated autophagy protein 9A (Atg9A)
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• inflammation of the stomach mucosa
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• heterozygotes display abnormal activation of autophagy
• EM of spinal cord neurons revealed large autophagosomes and autolysosomes and other features consistent with excessive or aberrant induction of autophagy; similar features are noted in brain and in isolated neurons
• LC3beta-positive neurons are detected in the spinal cord, indicating ongoing autophagy, unlike in wild-type controls
• heterozygous mutant MEFs show enlarged ER and aberrant autophagic structures, increased levels of autophagy markers, and decreased levels of the autophagy cargo protein p62; the autophagy phenotype can be rescued after expression of a dominant gain-of-acetylation mutant form of the ER-associated autophagy protein 9A (Atg9A)
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• when housed in an open facility, heterozygotes show increased plasma concentrations of several chemokines and cytokines, including IL-7, IL-18, CXCL6, CCL9 (MIP-3beta), and CCL19 (MIP-1gamma)
• in contrast, serum levels of CCL22, which is chemotactic for dendritic cells, monocytes, and chronically activated T cells, are significantly reduced
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• heterozygotes exhibit a ~50% decrease of acetyl-CoA transport across the ER membrane
• reduced influx of acetyl-CoA influx into the ER lumen is accompanied by reduced acetylation of ER proteins
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• inflammation of the bladder mucosa
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• inflammation of the prostate parenchyma
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• inflammation of the preputial gland
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• when housed in an open facility, adult heterozygotes exhibit severe ulcerative dermatitis
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• inflammation of the prostate parenchyma
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• inflammation of the preputial gland
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• when housed in an open facility, adult heterozygotes exhibit severe conjunctivitis
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• focal pulmonary adenoma
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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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