Analysis Tools|
Allele Symbol Allele Name Allele ID |
S1pr2tm1Ajml targeted mutation 1, A John MacLennan MGI:2180817 |
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| Summary |
3 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 66% of mice develop clonal B-cell lymphoma by 18-24 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| non-Hodgkin lymphoma | DOID:0060060 |
OMIM:605027 |
J:154439 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: on a 50:50 129SvEvBrd:C57BL/6 background homozygotes exhibit a ~15% overall death rate from seizures; however, on a pure 129SvEvBrd background the overall death rate drops below 5%
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• 42.9% of aging homozygotes (aged 70 days or older) exhibit impaired swimming ability, in the absence of overt motor dysfunction
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• Background Sensitivity: on a 50:50 129SvEvBrd:C57BL/6 background, some homozygotes display rare (mean <4 during lifespan), brief (mean <5 s) seizures; on a pure 129SvEvBrd background, the period of seizure susceptibility is reduced by ~75%; no seizures and death are noted on a purified C57BL/6NCrlBr background
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• occasional otosclerosis is detected well after the onset of hearing loss
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• in some cases, Reissner's membrane exits distant from its typical emergence from the upper limit of the stria vascularis
• in other cases, it appears to be partially collapsed over the stria vascularis
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• Rosenthal's canal is progressively and completely depleted of cell bodies and processes with increasing age
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• cochlear OHCs are lost with increasing age to a greater extent than in control inner ears
(J:112371)
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• by 3 weeks, the tunnel of Corti/Nuel's space structures are consistently abnormal
• with time, many structures of the organ of Corti are completely lost
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• aging homozygotes exhibit a much thinner stria vascularis
(J:112371)
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• in older homozygotes, the tectorial membrane is encased in a membrane-like cover, shows fiber-like striations, and is tilted from the site where the organ of Corti would lie
• commonly, epithelial-like cells form "nests" at the site where Reissner's membrane and the tectorial membrane lie together in both basal and apical cochlear turns
• basal cochlear turns are more affected, consistent with the only ABR signal from mutant mice being in response to the lowest frequency tone
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• the scala media portion of the cochlear labyrinth is reduced with increasing age
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• at one year, homozygotes display significant saccular degeneration
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• aging homozygotes display decreases in the otoconia of both the utricle and saccule relative to age-matched controls
(J:112371)
• loss of utricular otoconia precedes the vestibular defects (head tilt and swimming) and does not predict the behavioral defects as well as the loss of saccular otoconia
(J:112371)
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• homozygotes show no ABR responses at 100 dB (highest intensity tested); the threshold, were there to be any response, would thus be >100 dB
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• as early as P22, 100% of homozygotes are profoundly deaf, as shown by lack of auditory evoked brainstem (ABR) responses, while the vestibular defects are present in 40-50% of mutant mice
(J:112371)
• at P22, one homozygote showed a slight response to very high intensity (90 dB) 8 kHz tones but failed to respond to 100 dB clicks, 16 kHz tones or 32 kHz tones; all other homozygotes failed to respond to all tones and clicks
(J:112371)
• both old and young homozygotes fail to display any of the expected ABR peaks, suggesting defects in peripheral components of the auditory system
(J:112371)
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• aging homozygotes show signs of vestibular dysfunction e.g. head tilt and impaired swimming
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• Background Sensitivity: on a 50:50 129SvEvBrd:C57BL/6 background, some homozygotes display rare (mean <4 during lifespan), brief (mean <5 s) seizures; on a pure 129SvEvBrd background, the period of seizure susceptibility is reduced by ~75%; no seizures and death are noted on a purified C57BL/6NCrlBr background
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• cochlear OHCs are lost with increasing age to a greater extent than in control inner ears
(J:112371)
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• occasional otosclerosis is detected well after the onset of hearing loss
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• occasional otosclerosis is detected well after the onset of hearing loss
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autosomal recessive nonsyndromic deafness 68 | DOID:0110519 |
OMIM:610419 |
J:231927 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• unexpectedly, homozygotes display normal brain cytoarchitecture, peripheral axon growth and neurological development, with no postnatal motor/sensory dysfunction or defects in hippocampal and neocortical development
• however, between 3 and 7 wks of age, homozygotes display spontaneous, intermittent sporadic seizures of variable timing occurring in clusters of 3 or more per hr during 1-4-day periods within the susceptible interval
• ~85% of seizures are characterized by 2-10-sec wild running episodes followed by 15-60-sec periods of freezing
• the vast majority of severely affected homozygotes survive the susceptible period and recover
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• ~15% of seizures are characterized by 2-10 sec wild running episodes followed by tonic-clonic convulsions; 2% of these are lethal
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• under current clamp, 10 of 14 mutant neocortical pyramidal neurons exhibit spontaneous paroxysmal depolarizing shifts and bursts of action potentials
• addition of GABAA receptor antagonist bicuculline methiodide increases burst frequency and results in a prolonged depolarization with repetitive action potentials in 4 of the cells
• in the presence of bicuculline, electrically evoked epileptiform depolarization responses are augmented in mutant cells relative to wild-type cells
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• spontaneous seizures are accompanied by ictal-like EEG abnormalities and hyperexcitable neocortical pyramidal neurons
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• homozygotes show significant increases in both the frequency and amplitude of spontaneous EPSCs
• the ampliture of electrically evoked EPSCs is also markedly increased in the absence of pharmacological or ionic enhancement
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• of spontaneous EPSCs
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• of spontaneous EPSCs
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• unexpectedly, homozygotes display normal brain cytoarchitecture, peripheral axon growth and neurological development, with no postnatal motor/sensory dysfunction or defects in hippocampal and neocortical development
• however, between 3 and 7 wks of age, homozygotes display spontaneous, intermittent sporadic seizures of variable timing occurring in clusters of 3 or more per hr during 1-4-day periods within the susceptible interval
• ~85% of seizures are characterized by 2-10-sec wild running episodes followed by 15-60-sec periods of freezing
• the vast majority of severely affected homozygotes survive the susceptible period and recover
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• ~15% of seizures are characterized by 2-10 sec wild running episodes followed by tonic-clonic convulsions; 2% of these are lethal
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• increase in germinal center B cells in 9-12 month old mice before tumor formation
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• increase in germinal center CD69+ T cells in 9-12 month old mice before tumor formation
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• spleens show an increase in number of spontaneous germinal centers at 9-12 months of age before tumor formation
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• spleens show an increase in size of spontaneous germinal centers at 9-12 months of age before tumor formation
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• benign splenic marginal zone hyperplasia
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• increase in germinal center B cells in 9-12 month old mice before tumor formation
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• increase in germinal center CD69+ T cells in 9-12 month old mice before tumor formation
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• spleens show an increase in number of spontaneous germinal centers at 9-12 months of age before tumor formation
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• spleens show an increase in size of spontaneous germinal centers at 9-12 months of age before tumor formation
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• benign splenic marginal zone hyperplasia
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• mice develop clonal B-cell lymphomas with age, such that 50% of mice show neoplasm by 1.5-2 years of age
• tumors show features of germinal center-derived diffuse large B-cell lymphoma
• tumors are seen in mesenteric, submandibular, and mediastinal lymph nodes, in the spleen, and rarely in the liver and retroperitoneal soft tissue, with frequent involvement of multiple sites within individual mice
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• a very low incidence of lung tumors is seen and these are adenocarcinomas or very large lung adenoma classified as carcinoma due to size
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• a very low incidence of lung tumors is seen and these are adenocarcinomas or very large lung adenoma classified as carcinoma due to size
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| non-Hodgkin lymphoma | DOID:0060060 |
OMIM:605027 |
J:154439 | |
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 12/10/2024 MGI 6.24 |
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