Phenotypes associated with this allele

• Allele Symbol: Tlx1^tm1Sjk
• Allele Name: targeted mutation 1, Stanley J Korsmeyer
• Allele ID: MGI:1857260
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tlx1^tm1Sjk/Tlx1^tm1Sjk	involves: 129S2/SvPas	MGI:2668994
cx2	Tlx1^tm1Sjk/Tlx1^tm1Sjk Tlx3^tm1Sjk/Tlx3^tm1Sjk	involves: 129S2/SvPas * 129X1/SvJ	MGI:3807393

Genotype
MGI:2668994

hm1

• Allelic Composition: Tlx1^tm1Sjk/Tlx1^tm1Sjk
• Genetic Background: involves: 129S2/SvPas

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

hematopoietic system

increased number of Howell-Jolly bodies ( J:17695 )

• many erythrocytes contain nuclear fragments of condensed DNA known as Howell-Jolly bodies, commonly associated with asplenia

• however, complete blood counts indicate that the number of red blood cells is normal

increased leukocyte cell number ( J:17695 )

• homozygotes display a ~2-fold increase in the number of white blood cells relative to wild-type mice

• however, the B-cell and T-cell profile is normal in thymus, lymph node and peripheral blood

increased neutrophil cell number ( J:17695 )

• in peripheral blood smears

increased lymphocyte cell number ( J:17695 )

• in peripheral blood smears

abnormal spleen development ( J:17695 )

• at E12.5, mutant embryos display no cellular organization or mesenchymal cell condensation at the site of splenic development

• at E13.5, mutant embryos show no histological evidence of a splenic primordium within the dorsal mesogastrium

abnormal spleen mesenchyme morphology ( J:17695 )

• at E12.5, mutant embryos display no mesenchymal cell condensation at the site of splenic development, indicating a specific, localized defect in mesodermal cells destined to form the spleen

absent spleen ( J:17695 )

• all adult homozygotes appear externally normal but display complete absence of spleen

• in contrast, all other internal organs (including the stomach and pancreas) are normal in morphology and position

immune system

increased leukocyte cell number ( J:17695 )

• homozygotes display a ~2-fold increase in the number of white blood cells relative to wild-type mice

• however, the B-cell and T-cell profile is normal in thymus, lymph node and peripheral blood

increased neutrophil cell number ( J:17695 )

• in peripheral blood smears

increased lymphocyte cell number ( J:17695 )

• in peripheral blood smears

abnormal spleen development ( J:17695 )

• at E12.5, mutant embryos display no cellular organization or mesenchymal cell condensation at the site of splenic development

• at E13.5, mutant embryos show no histological evidence of a splenic primordium within the dorsal mesogastrium

abnormal spleen mesenchyme morphology ( J:17695 )

• at E12.5, mutant embryos display no mesenchymal cell condensation at the site of splenic development, indicating a specific, localized defect in mesodermal cells destined to form the spleen

absent spleen ( J:17695 )

• all adult homozygotes appear externally normal but display complete absence of spleen

• in contrast, all other internal organs (including the stomach and pancreas) are normal in morphology and position

embryo

embryo phenotype ( J:17695 )

N • despite observed gene expression in the branchial region of wild-type mice, homozygotes display no detectable abnormalities in branchial arches

nervous system

nervous system phenotype ( J:17695 )

N • despite observed gene expression in the developing hindbrain and cranial ganglia of wild-type mice, homozygotes display no detectable abnormalities in the hindbrain, cranial ganglia or cranial motor nuclei

Genotype
MGI:3807393

cx2

• Allelic Composition: Tlx1^tm1Sjk/Tlx1^tm1Sjk; Tlx3^tm1Sjk/Tlx3^tm1Sjk
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ

nervous system

abnormal sensory neuron morphology ( J:76655 )

• 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

abnormal sensory neuron innervation pattern ( J:76655 )

• 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

abnormal spinal cord morphology ( J:134327 )

• 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

abnormal dorsal interneuron morphology ( J:76655 )

• 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 Tlx3^tm1Sjk homozygotes

• however, no enhanced cell death is detected in E11.5-E14.5 double mutant embryos, as shown by TUNEL analysis

abnormal dorsal interneuron 2 morphology ( J:76655 )

abnormal dorsal interneuron 4 morphology ( J:76655 )

abnormal spinal cord dorsal horn morphology ( J:134327 )

• number of somatostatin expressing neurons is reduced 5-fold in dorsal spinal cord at E18.75 due to absence of somatostatin in dorsal horn