Phenotypes associated with this allele

• Allele Symbol: Otx2^tm6Asim
• Allele Name: targeted mutation 6, Antonio Simeone
• Allele ID: MGI:2661065
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Otx2^tm6Asim/Otx2^tm11Asim Slc6a3^tm1.1(cre)Bkmn/Slc6a3^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:4887467
cn2	Otx2^tm1.1(cre/ERT2)Mgoe/Otx2^tm6Asim Tg(CAG-cat,-EGFP)1Rbns/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:5473338
cn3	Otx1^tm4(cre)Asim/Otx1^+ Otx2^tm6Asim/Otx2^tm6.1Asim	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:2661066
cn4	Gdf7^tm3(cre)Tmj/Gdf7^+ Otx2^tm6Asim/Otx2^tm6Asim Tg(CAG-cat,-EGFP)1Rbns/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5473339

Genotype
MGI:4887467

cn1

• Allelic Composition: Otx2^tm6Asim/Otx2^tm11Asim; Slc6a3^{tm1.1(cre)Bkmn}/Slc6a3⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

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

nervous system

increased susceptibility to dopaminergic neuron neurotoxicity ( J:166896 )

• MPTP-treated mice exhibit reduced numbers of tyrosine hydroxylase (TH)+ neurons and GFP+ TH+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with similarly treated wild-type mice

abnormal neuron differentiation ( J:166896 )

• the percentage of GFP+ glyco-Slc6a3 (DAT)+ neurons is higher than in control mice

homeostasis/metabolism

increased susceptibility to dopaminergic neuron neurotoxicity ( J:166896 )

• MPTP-treated mice exhibit reduced numbers of tyrosine hydroxylase (TH)+ neurons and GFP+ TH+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with similarly treated wild-type mice

cellular

increased susceptibility to dopaminergic neuron neurotoxicity ( J:166896 )

• MPTP-treated mice exhibit reduced numbers of tyrosine hydroxylase (TH)+ neurons and GFP+ TH+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with similarly treated wild-type mice

abnormal neuron differentiation ( J:166896 )

• the percentage of GFP+ glyco-Slc6a3 (DAT)+ neurons is higher than in control mice

Genotype
MGI:5473338

cn2

• Allelic Composition: Otx2^{tm1.1(cre/ERT2)Mgoe}/Otx2^tm6Asim; Tg(CAG-cat,-EGFP)1Rbns/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

nervous system

abnormal choroid plexus morphology ( J:194049 )

• when tamoxifen is given on E15, choroid epithelial cells as well as the entire structures appear unaltered in size; however, at P7, fourth ventricular choroid plexus is much smaller (decreased rostrocaudally, not lateral to medial) compared to controls

absent choroid plexus ( J:194049 )

• with tamoxifen induction on E9 of gestation, the four choroid plexuses in the forebrain (including the third ventricular choroid plexus anlage) and hindbrain are virtually absent in E13 embryos; in some embryos a small remnant is found caudally but this tissue is not transthyretin-positive as expected

Genotype
MGI:2661066

cn3

• Allelic Composition: Otx1^tm4(cre)Asim/Otx1⁺; Otx2^tm6Asim/Otx2^tm6.1Asim
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

mortality/aging

neonatal lethality, complete penetrance ( J:83110 )

• all mutants die at birth

nervous system

abnormal neuronal precursor proliferation ( J:83110 )

• proliferating neuroblasts are increased in number in floor plate neuroepithelium at E12.5

abnormal midbrain-hindbrain boundary morphology ( J:83110 )

• isthmus is reduced in size and thickness at E18.5

small tectum ( J:83110 )

• posterior tectum is reduced in size and thickness at E18.5

abnormal tegmentum morphology ( J:83110 )

• tegmentum is enlarged at E18.5

cellular

abnormal neuronal precursor proliferation ( J:83110 )

• proliferating neuroblasts are increased in number in floor plate neuroepithelium at E12.5

Genotype
MGI:5473339

cn4

• Allelic Composition: Gdf7^tm3(cre)Tmj/Gdf7⁺; Otx2^tm6Asim/Otx2^tm6Asim; Tg(CAG-cat,-EGFP)1Rbns/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

abnormal choroid plexus morphology ( J:194049 )

• by E13, a dramatic decrease in hindbrain choroid plexus size is detected relative to controls

• at P2 and adult ages, the choroid plexus is much smaller than in controls

• increased apoptosis (both late and early, overall a 2.5 fold increase) is detected in the hindbrain choroid at E13.5; less proliferating cells are also detected in the plexus compared to controls

• blood vessels form at normal density, although they appear slightly more disorganized in the hindbrain choroid plexus region

abnormal cerebral cortex morphology ( J:194049 )

• at E13, an increase in apical PH3-positive cells is observed (30%) with a slight decrease in basal progenitors (10%); a 40% decrease in PH3-ve cells at the apical surface is detected in the cerebral cortex at P16

abnormal nervous system physiology ( J:194049 )

• total CSF protein concentration is increased by 30% and 60% at E13 and E14 relative to control values; at E12, no change is detected