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Allele Symbol Allele Name Allele ID |
Plxnb2tm1Matl targeted mutation 1, Marc Tessier-Lavigne MGI:3620317 |
| Summary |
15 genotypes |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• migration of granule cell precursors from explants cultured on laminin or laminin and Sema4c is impaired compared to in wild-type explants
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• migration of granule cell precursors from explants cultured on laminin or laminin and Sema4c is impaired compared to in wild-type explants
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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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• Background Sensitivity: penetrance of neonatal lethality is increased in mice on an inbred C57BL/6 background compared to those on an outbred CD-1 background
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• Background Sensitivity: frequency of neural tube closure defects is higher on an inbred C57BL/6 background compared to mice on an outbred CD-1 background
• Background Sensitivity: defects in posterior neuropore closure result in curled tail or spina bifida in 45% (9 of 20) of embryos
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• at E8.5, neural head folds fail to fuse
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• in some embryos with more severe defects in posterior neuropore closure
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• seen in 90% (18 of 20) of embryos
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• at E16.5, 9.3% of embryos exhibit unilateral double renal pelvises
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• at E16.5, kidneys are consistently smaller than wild-type or heterozygous kidneys
• skeleton images derived from E12.5 kidneys cultured overnight show a 25% reduction in kidney length relative to wild-type controls
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• reduced renal size is first seen at E12 and persists to at least E16.5 (last stage examined)
• however, E13.5 kidneys show normal expression patterns of markers for mesenchymal, epithelial, vascular and stromal structures
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• at E11.5-E16.5, 9.3% of embryos exhibit unilateral double ureters and kidneys, unlike in wild-type or heterozygous controls
• the size and extent of ureteric branching of each individual kidney in the double kidney complex is similar to that in the contralateral kidney
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• at E11.5-E16.5, 9.3% of embryos exhibit unilateral double ureters and kidneys, unlike in wild-type or heterozygous controls
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• at E12.5, kidneys show an intrinsic defect of the ureteric epithelium that results in fewer branches and reduced proliferation
• isolated ureteric buds (UBs) fail to branch and grow in matrigel in response to GDNF, even after 4 days in culture; however, the response to GDNF is rescued by the addition FGF7 and follistatin
• kidney explants fail to respond semaphorin 4C (a ligand for Plexin B2) by branching of the ureteric epithelium, whereas SEMA4C increases the number of tips by 16% in wild-type and by 40% in heterozygous explants
• however, isolated E12.5 UB cells adhere to and spread normally on different substrates (e.g. laminin and fibronectin) with a normal pattern of actin cytoskeleton and focal adhesions, while E12.5 kidneys show normal organization of the actin cytoskeleton in the stalks and tips of the ureteric epithelium
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• at E12.5, kidneys show 40% less ureteric bud tips than wild-type or heterozygous kidneys
• ureteric tip cells proliferate 10% less than in heterozygous and 9% less than in wild-type kidneys, as shown by BrdU staining
• however, no change in the rate of apoptosis is detected in the ureteric epithelium, based on a TUNEL assay
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• Background Sensitivity: frequency of neural tube closure defects is higher on an inbred C57BL/6 background compared to mice on an outbred CD-1 background
• Background Sensitivity: defects in posterior neuropore closure result in curled tail or spina bifida in 45% (9 of 20) of embryos
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• at E8.5, neural head folds fail to fuse
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• in some embryos with more severe defects in posterior neuropore closure
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• Background Sensitivity: in some embryos with mild defects in posterior neuropore closure
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• white patches along the ventral midline
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• white patches along the ventral midline
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Perturbed olfactory bulb layering and proliferation in the Plxnb2tm1Matl/Plxnb2tm1Matl mice
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• Background Sensitivity: penetrance of neonatal lethality is decreased in mice on an outbred CD-1 background compared to those on an inbred C57BL/6 background
• Background Sensitivity: after 4 generations of outcrossing 30% of mice are viable and fertile
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| N |
• after 4 generations of outcrossing 30% of mice are viable and fertile
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• at P11 the palisade of radial glial cells is perturbed and fibers of glial cells are curved and take irregular courses
• however, fibers still extend to the pial surface and form characteristic end feet, at E18 there are no major difference in radial glia cell organization, and radial cell migration does not appear to be altered,
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• BrdU labeling and GFP electroporation into postnatal subventricular zone (SVZ) revealed increased radial migration in the OB, as SVZ-derived neuroblasts leave the RMS more rapidly than in heterozygous controls
• time-lapse analysis of GFP-labeled cells in the RMS of P7 forebrain slices showed a 40% increase in the average speed of migrating neuroblasts relative to heterozygous controls
• a fraction of neuroblasts migrate ectopically into the septum and corpus callosum
• however, neurite length is not significantly altered and in vitro migration of SVZ neuroblasts in response to GDNF and HGF is normal in explant cultures
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• adult mice show a significant reduction in the number of proliferating BrdU+ cells at different rostrocaudal levels along the SVZ-RMS-OB pathway, that is more pronounced in the caudal ventricular region (-44%) and rostral ventricle (-39%) than in the transition region (-30%) or the OB (-27%) relative to heterozygous controls
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• at 4 days after BrdU injection, 73% of BrdU-labeled cells have reached the OB versus 63.5% in heterozygous controls
• only 87.5% of BrdU+ cells are found in the rostral migratory stream (RMS) while >12.5% are detected in the GC and PG layers, unlike in heterozygous controls where >95% of BrdU+ cells are found in the RMS and only 5% have migrated radially out of the RMS and entered the GC layer
• similarly, OB interneurons labeled with GFP enter the PG and GC layers more rapidly than in heterozygous controls
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• mice exhibit impaired generation of new OB interneurons with periglomerular cells being more affected than granule cells
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• in a 30-day BrdU incorporation assay, adult mice show a 35% reduction in the number of BrdU+ granule cells (GCs) per OB section relative to heterozygous controls
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• in a 30-day BrdU incorporation assay, adult mice show a 51% reduction in the number of BrdU+ periglomerular cell (PGs) per OB section relative to heterozygous controls
• ratio between the average number of GC and PG cells per OB section is higher than that in heterozygous controls (16.2:1 versus 11.8:1, respectively), suggesting that PG cells are more affected than GC cells
• the number of calretinin-positive PG cells is reduced by 19.5% relative to heterozygous controls
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• adult mice exhibit perturbed olfactory bulb (OB) layering
• however, OB volume is normal
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• the inner plexiform layer is not clearly distinguishable
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• the mitral cell layer is not clearly distinguishable
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• severe defects in cerebellar gross morphology
• proliferating granule cells are scattered throughout the external glial cell layer and in the cerebellar parenchyma but by P0 the number of mitotic cells in the external glial cell layer and cerebrum is slightly lower
• however, no increase in cell death was detected in P15 cerebellums and no proliferating cells detected in mice P27 or older
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• mice have less compact and disorganized external granule cell layer (EGL) architecture
• the upper and lower EGL often overlap and many migrating postmitotic granule cells reaching the pial surface
• at P0, proliferating granule cells are scattered throughout the EGL and also in the cerebellar parenchyma, rather than being primarily confined to the upper EGL as in heterozygous controls
• at P0, the number of mitotic cells in the EGL is slightly lower; however, at P13 and P15 a significant increase in cell proliferation is detected
• however, no increase in cell death was detected in P15 cerebellums and no proliferating cells are detected in mice at or after P27
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• fragmented into multiple groups or islands of Purkinjie cells
• however, climbing fibers still contact Purkinje cells and mossy fiber rosettes are only found next to granule cells
• at P0, PLAP-expressing cells (parallel fibers) are intermingled with CaBP-positive Purkinje cells within the cerebellar plate, rather than confined to the upper external granule layer
• however, interneurons are in their usual positions, maintain their usual connections and some typical basket cell 'pinceaux' are observed at the base of Purkinje cell somata
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• absence of precentral and intercrural fissures, other fissures are less pronounced, lobules I-III and VI-VII are fused and most folia are irregular
a midline cleft in lobule X is present
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• some Purkinje cells are found in the white matter
• at P12 rings of proliferating granule cells are found at the periphery of Purkinje cells islands
• however, parallel fibers are confined to Purkinje dendrites in the ectopic islands and in the molecular layer in the less affected folia
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• some Purkinje cells are found in the white matter
• at P12 rings of proliferating granule cells are found at the periphery of Purkinje cells islands
• however, parallel fibers are confined to Purkinje dendrites in the ectopic islands and in the molecular layer in the less affected folia
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• perturbation in the granule layer occur mainly in the rostral and caudal folia
• the granule layer is almost completely absent from the base of some folia and its architecture is disorganized with cells from upper and lower layers intermingling
• however, the overall arrangement of cerebral neurons and axons is preserved
• the base of some folia lack the cerebellar granule layer
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• in adults, ectopic clusters of granule cells are present with some granule cells invading the deep nuclei
• however, in less affected folia only a few ectopic granule cells are observed and ectopic clusters may not be equivalent to granule cell progenitor
• at P0, post mitotic granule cells are found deep within the cerebellar parenchyma
• at P12 rings of proliferating granule cells are found at the periphery of Purkinje cells islands
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• there is a 65-100% decrease in cerebellum size compared to wild-type mice
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| N |
• despite abnormalities in the morphology of the cerebellum, mice exhibit no behavioral or motor deficits
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• at P11 the palisade of radial glial cells is perturbed and fibers of glial cells are curved and take irregular courses
• however, fibers still extend to the pial surface and form characteristic end feet, at E18 there are no major difference in radial glia cell organization, and radial cell migration does not appear to be altered,
|
|
• BrdU labeling and GFP electroporation into postnatal subventricular zone (SVZ) revealed increased radial migration in the OB, as SVZ-derived neuroblasts leave the RMS more rapidly than in heterozygous controls
• time-lapse analysis of GFP-labeled cells in the RMS of P7 forebrain slices showed a 40% increase in the average speed of migrating neuroblasts relative to heterozygous controls
• a fraction of neuroblasts migrate ectopically into the septum and corpus callosum
• however, neurite length is not significantly altered and in vitro migration of SVZ neuroblasts in response to GDNF and HGF is normal in explant cultures
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• adult mice show a significant reduction in the number of proliferating BrdU+ cells at different rostrocaudal levels along the SVZ-RMS-OB pathway, that is more pronounced in the caudal ventricular region (-44%) and rostral ventricle (-39%) than in the transition region (-30%) or the OB (-27%) relative to heterozygous controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are born at Mendelian ratios and show no defects in neural tube closure
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• at E15.5, a higher fraction of neural progenitor cells (NPCs) have exited cell cycle in the cortex relative to controls (~60% versus ~40% BrdU+ Ki67- cells per total number of BrdU+ cells), indicating premature exhaustion of the progenitor pool; however, cleavage plane orientation of radial glial progenitors (RGPs) relative to the ventricular zone (VZ) surface is normal
• in culture, NPCs derived from E14.5 forebrains exhibit a higher rate of spontaneous neural differentiation, as shown by an increased fraction of Tuj1+ (neuronal) and GalC+ (oligodendrocytic) cells
• the multi-lineage differentiation potential of cultured NPCs is normal
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• at E15.5, the number of proliferating NPCs in the caudomedial cortex is reduced by ~30%, as shown by Ki67 or BrdU staining at the VZ
• at E15.5, the number of mitotic phosphorylated histone 3-labeled (pH3+) RGPs at the ventricular surface of the caudomedial cortex is reduced by 26% while the number of phosphorylated vimentin-labeled RGPs is reduced by 21.1%
• in culture, NPCs derived from E14.5 forebrains show a ~55% decrease in the proliferative index of Ki67+ Nestin+ progenitors as well as a significant reduction in Olig2+ progenitors
• however, no significant differences in apoptosis are noted in the caudomedial cortex at E12.5 or E15.5
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• at E15.5, the number of proliferating NPCs in the caudomedial cortex is reduced by ~30%, as shown by Ki67 or BrdU staining at the VZ
• at E15.5, the number of pH3+ RGPs at the ventricular surface of the caudomedial cortex is reduced by 26% while the number of phosphorylated
vimentin-labeled RGPs is reduced by 21.1%
• however, no defects are noted in the arrangement of apical cilia of VZ cells facing the ventricular lumen at E14.5
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• adult mice display underdevelopment of the rostral lobules with fusion of lobules 1-3, similar to Plxnb2tm1Matl homozygotes
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• at E15.5 and E17.5, lateral ventricles are often enlarged
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• adult brains display reduced size (thinning) of the corpus callosum
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• at P10, complete agenesis of the corpus callosum is often observed
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• at E15.5, cortical thickness and neuronal numbers are proportionally reduced in all layers, including germinal zones at the VZ/subventricular zone (SVZ) as well as distinct laminae in the cortical plate
• at E17.5, the number of early-born TBR1+ deep layer neurons is reduced by 34.6% in the caudomedial cortex; a similar reduction is noted in CTIP2+ deep layer cortical neurons
• at E17.5, the number of late-born SATB2+ upper layer neurons is reduced by 18.2%
• laminar organization of the cortex is normal at E17.5 and in adult mice
• no defects in lineage progression or overt radial or tangential migration defects are observed
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• cortical thinning begins at E12.5, becomes more obvious at E15.5 and E17.5, and is more severe in medial than lateral, and caudal than rostral cortical areas with a bias for the caudomedial cortex
• at E15.5, brains exhibit thinning of the medial cortex with a ~21% reduction in overall thickness
• adult brains show less thinning of the caudomedial cortex (~12% reduction)
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• adult mice display ectopias of granule cells in the molecular layer of caudal lobules, similar to Plxnb2tm1Matl homozygotes
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• at E15.5, the total number of SOX2+ neural progenitor cells in the caudomedial cortex is reduced by 19.2%
• at E15.5, the number of TBR2+ intermediate progenitor (IP) cells within the SVZ is reduced by 15%
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• at E15.5, a higher fraction of neural progenitor cells (NPCs) have exited cell cycle in the cortex relative to controls (~60% versus ~40% BrdU+ Ki67- cells per total number of BrdU+ cells), indicating premature exhaustion of the progenitor pool; however, cleavage plane orientation of radial glial progenitors (RGPs) relative to the ventricular zone (VZ) surface is normal
• in culture, NPCs derived from E14.5 forebrains exhibit a higher rate of spontaneous neural differentiation, as shown by an increased fraction of Tuj1+ (neuronal) and GalC+ (oligodendrocytic) cells
• the multi-lineage differentiation potential of cultured NPCs is normal
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• at E15.5, the number of proliferating NPCs in the caudomedial cortex is reduced by ~30%, as shown by Ki67 or BrdU staining at the VZ
• at E15.5, the number of mitotic phosphorylated histone 3-labeled (pH3+) RGPs at the ventricular surface of the caudomedial cortex is reduced by 26% while the number of phosphorylated vimentin-labeled RGPs is reduced by 21.1%
• in culture, NPCs derived from E14.5 forebrains show a ~55% decrease in the proliferative index of Ki67+ Nestin+ progenitors as well as a significant reduction in Olig2+ progenitors
• however, no significant differences in apoptosis are noted in the caudomedial cortex at E12.5 or E15.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are born at Mendelian ratios and show no defects in neural tube closure or cortical development
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• adult mice display migratory defects of neuroblasts in the rostral migratory stream, similar to Plxnb2tm1Matl homozygotes
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• adult mice display underdevelopment of the rostral lobules with fusion of lobules 1-3, similar to Plxnb2tm1Matl homozygotes
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• migrating cells in the rostral migratory stream (RMS) persist in chain formation after exiting the RMS, similar to Plxnb2tm1Matl homozygotes
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• adult mice display ectopias of granule cells in the molecular layer of caudal lobules, similar to Plxnb2tm1Matl homozygotes
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• adult mice display migratory defects of neuroblasts in the rostral migratory stream, similar to Plxnb2tm1Matl homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in a transwell assay with stromal cell line-derived factor-1alpha (SDF-1alpha) or brain derived neurotrophic factor (BDNF), granule cell precursors exhibit impaired migration compared with wild-type cells and cells form Sema4ctm1Matl homozygotes
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• the internal granule layer of lobules II and III is disrupted compared to in wild-type mice and more severely disrupted compared to in Sema4ctm1Matl homozygotes
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• in a transwell assay with stromal cell line-derived factor-1alpha (SDF-1alpha) or brain derived neurotrophic factor (BDNF), granule cell precursors exhibit impaired migration compared with wild-type cells and cells form Sema4ctm1Matl homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit a gap in the lobule X unlike wild-type mice and Sema4ctm1Matl homozygotes
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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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• in a transwell assay with stromal cell line-derived factor-1alpha (SDF-1alpha) or brain derived neurotrophic factor (BDNF), granule cell precursors exhibit impaired migration compared with wild-type cells and cells from Sema4gtm1Kik homozygotes
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• in a transwell assay with stromal cell line-derived factor-1alpha (SDF-1alpha) or brain derived neurotrophic factor (BDNF), granule cell precursors exhibit impaired migration compared with wild-type cells and cells from Sema4gtm1Kik homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• double homozygotes show high embryonic lethality prior to onset of nephrogenesis
• only 1 of 19 double homozygotes survived to E12.5
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• the single double homozygous embryo surviving to E12 showed hypoplastic kidneys with ureteric branches and differentiating mesenchyme
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• at E12, the ureteric stalks appear to be longer than in double heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are viable
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• mice are able to produce offspring although litters are very small
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are viable
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• mice are able to produce offspring although litters are very small
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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 07/02/2024 MGI 6.13 |
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