Phenotypes Associated with This Genotype

Genotype
MGI:3807393

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

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

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