Analysis Tools
nervous system
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• in dorsal horn, glutaminergic differentiation is almost completely abolished compared to wild-type
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Allele Symbol Allele Name Allele ID |
Tlx3tm1Sjk targeted mutation 1, Stanley J Korsmeyer MGI:2180105 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in dorsal horn, glutaminergic differentiation is almost completely abolished compared to wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygotes develop to term but die shortly after birth from a central respiratory failure
• homozygotes die from hypoventilation within 24 hrs of birth, even when respiration is transiently initiated by mechanical stimulation
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• C4 vetral root recordings in medulla-spinal cord preparations from newborn homozygotes reveal a rapid respiratory rate with shorter inspiratory duration and intermittent respiratory arrest of ~7.4 sec in duration relative to wild-type controls
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• during non-apnea periods, homozygotes display an increased respiratory rate relative to wild-type mice
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• most newborn homozygotes display immediate apnea
• electromyographic activity of intercostal muscles indicates a high incidence of apnea episodes of up to 20 sec in duration
• mutant pups exhibit an average of ~13 apnea episodes of more than or equal to 5 sec during 10 min of observation relative to only 1 episode in wild-type mice
• the average duration of an apnea episode is nearly doubled in mutant mice relative to wild-type mice
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| N |
• homozygotes show no major histopathologic abnormalities in cranial sensory neurons and brain nuclei
• no significant neuron loss or gliosis is observed
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• homozygotes display abnormal D2 interneuron development, as suggested by loss of Isl1 expression (a marker for D2 interneurons) in the dorsal spinal cord at E11.5
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• homozygotes display abnormal D4 interneuron development in the caudal spinal cord, as indicated by expression loss of both Lmx1b and Phox2a in ventrally migrating D4 interneurons at E11.5; in contrast, the most dorsal Lmx1b expression is unaffected
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• newborn homozygotes display a functional disorder in the central pattern generator of respiration in the ventral medulla
• a coordinate pattern is observed in which failure of inspiratory neuron firing correlates with the respiratory arrest measured as C4 ventral root activity
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• newborn homozygotes always lack gastric milk
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| N |
• newborn homozygotes display fully developed spleens
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| N |
• newborn homozygotes do not display colonic abnormalities
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| congenital central hypoventilation syndrome | DOID:0060731 |
OMIM:209880 |
J:60751 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at hindlimb level, reduction in glutaminergic neurons observed in Lbx1 mutants is reversed
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• at age E12.5, neurons expressing GABAergic markers are reduced in dorsal spinal cord; similar to phenotype observed in Lbx1-single mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• double homozygotes exhibit improper development of most relay somatic sensory neurons, including the spinal-trigeminal nucleus, the dorsal horn of the spinal cord, and a portion of the principle trigeminal nucleus, as indicated by the loss or reduction of expression of specific molecular markers, and by the failure of ingrowth of trkA+ afferents to the trigeminal nucleus and the dorsal horn of the spinal cord
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• at E14.5, trkA+ nociceptive/thermoceptive sensory afferents from double homozygous mutant mice are able to reach the dorsal entry zone but fail to enter the dorsal horn, unlike wild-type trkA+ afferents which start forming collateral branches into the spinal cord
• at E18.5, the ingrowth of trkA+ afferents in the double mutant spinal cord is much shallower than the projections noted in wild-type embryos; a similar defect is observed in the ingrowth of cranial trkA+ afferents to the spinal-trigeminal nucleus
• in contrast, projection of a subset of trkA+ afferents to the deep laminae of the spinal cord appears normal
• also, neuronal migration of dorsal horn neurons appears unaffected, as suggested by similar BrdU pulse-chase labeling patterns in wild-type and double mutant embryos
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• at E14.5, number of somatostatin expressing neurons in dorsal spinal cord is increased 5-fold compared to wild-type embryos; most of the increase in neurons is confined to intermediate and deep dorsal laminas
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• double homozygotes exhibit improper formation of two classes of dorsal interneurons, D2 and D4, as indicated by loss of specific marker (Isl1 and Lmx1b) expression
• double homozygotes display defective medullary D4 interneuron formation, as indicated by expression loss of both Lmx1b and Phox2a in the lateral area; not observed in single Tlx3tm1Sjk homozygotes
• however, no enhanced cell death is detected in E11.5-E14.5 double mutant embryos, as shown by TUNEL analysis
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• number of somatostatin expressing neurons is reduced 5-fold in dorsal spinal cord at E18.75 due to absence of somatostatin in dorsal horn
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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 04/16/2024 MGI 6.23 |
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