Phenotypes associated with this allele

• Allele Symbol: Numb^tm1Ynj
• Allele Name: targeted mutation 1, Yuh Nung Jan
• Allele ID: MGI:1932085
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Numb^tm1Ynj/Numb^tm1Ynj	involves: 129X1/SvJ	MGI:3789961
cn2	Emx1^tm1(cre)Krj/Emx1^+ Numb^tm1Ynj/Numb^tm1Ynj	involves: 129S2/SvPas * 129X1/SvJ * CD-1	MGI:3582334
cn3	Emx1^tm1(cre)Krj/Emx1^+ Numb^tm1Ynj/Numb^tm1Ynj Numbl^tm1Wmz/Numbl^tm1Wmz	involves: 129S2/SvPas * 129X1/SvJ * CD-1	MGI:3582335
cn4	Numb^tm1Ynj/Numb^tm1Ynj Numbl^tm1Wmz/Numbl^tm1Wmz Tg(Nes-cre)1Wmz/0	involves: 129X1/SvJ	MGI:2451225
cn5	Numb^tm1Ynj/Numb^tm1Ynj Tg(Nes-cre)1Wmz/0	involves: 129X1/SvJ	MGI:2451227
cn6	Numb^tm1Ynj/Numb^tm1Ynj Numbl^tm1Wmz/Numbl^tm1Wmz Tg(Nes-cre/Esr1*)4Ynj/0	involves: 129X1/SvJ * C57BL/6	MGI:3765970

Genotype
MGI:3789961

hm1

• Allelic Composition: Numb^tm1Ynj/Numb^tm1Ynj
• Genetic Background: involves: 129X1/SvJ

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

normal phenotype

no abnormal phenotype detected ( J:62712 )

• mice are viable and indistinguishable from wild-type littermates

Genotype
MGI:3582334

cn2

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Numb^tm1Ynj/Numb^tm1Ynj
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * CD-1

normal phenotype

no abnormal phenotype detected ( J:87149 )

• viable and fertile with no detectable phenotypes

Genotype
MGI:3582335

cn3

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Numb^tm1Ynj/Numb^tm1Ynj; Numbl^tm1Wmz/Numbl^tm1Wmz
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * CD-1

mortality/aging

postnatal lethality, incomplete penetrance ( J:87149 )

• animals that were small tended to die between P5 and P21

behavior/neurological

stereotypic behavior ( J:87149 )

• mutants that survived to adulthood appeared jittery

circling ( J:87149 )

• 25% of the mutants displayed circling behavior

social withdrawal ( J:87149 )

• mutants that survived to adulthood appeared to have normal life span but were solitary

sporadic seizures ( J:87149 )

• mutants that survived to adulthood exhibited sporadic seizures

growth/size/body

decreased body size ( J:87149 )

• most mutant mice were slightly smaller than controls but were within the normal range of sizes and survived to adulthood

• occasionally, they reached only about one-third the size of their littermates

nervous system

sporadic seizures ( J:87149 )

• mutants that survived to adulthood exhibited sporadic seizures

increased neuron apoptosis ( J:87149 )

• TUNEL staining of E14.5 embryonic brain sections suggest that increased cell death may contribute to the loss of mature neurons

abnormal neuron differentiation ( J:87149 )

• several experiments indicate that neural progenitor cell proliferation increased drastically in the mutant region

• starting from E10.5, Nestin-positive progenitor cells in the mutant showed very little radial organization

• mutant neural progenitor cells were organized into multiple clusters of neurogenic foci across the cortex and did not migrate to the outer layer of the cortex

abnormal embryonic neuroepithelium morphology ( J:87149 )

• by E10.5, the neuroepithelium in the dorsal forebrain was noticeably undulating

abnormal brain ventricle morphology ( J:87149 )

• rough ventricular surfaces in mutant brains are suggestive of the shedding of brain tissues into the ventricle; shed tissues were occasionally found in the lateral ventricles

enlarged brain ventricles ( J:87149 )

• extensive ventricular enlargement

abnormal forebrain morphology ( J:87149 )

• by E10.5, the neuroepithelium in the dorsal forebrain was noticeably undulating

• at E12.5, the forebrain exhibited undulating, folding, and invaginating with clumps of cells peeling into the lateral ventricle from the apical surface of the cortical ventricular zone

abnormal cortical marginal zone morphology ( J:87149 )

• marginal zone absent and displayed no discernible laminar structures

• contained numerous cell clusters

abnormal lateral ventricle morphology ( J:87149 )

• shed tissues were occasionally found in the lateral ventricles

absent corpus callosum ( J:87149 )

• no identifiable corpus callosum in the caudodorsal region while corpus callosum in the rostral region was relatively normal

small thalamus ( J:87149 )

• small thalamus

abnormal hippocampus morphology ( J:87149 )

abnormal cerebral cortex morphology ( J:87149 )

• overgrown caudodorsal neocortex and thinning of the lateral cortex

• in extreme cases, the caudodorsal region was nearly missing, with just a thin layer of the cortex remaining with extreme ventricular enlargement

• the volume of the mutant cortex was increased

abnormal neuron specification ( J:87149 )

• reduction in the number of mature neurons later in the double mutant animal was revealed by reduced expression of neuronal markers

ectopic cortical neuron ( J:87149 )

• multidendritic neurons, normally located in layer I, were distributed all over the mutant cortex

• Cajal-Retzius cells were displaced from the normal location in the outer layer of the neocortex to the ectopic sites across the cortex

reproductive system

female infertility ( J:87149 )

♀

male infertility ( J:87149 )

♂

hearing/vestibular/ear

abnormal hearing physiology ( J:87149 )

• 25% of the mutants displayed hypersensitivity to sound stimuli

embryo

abnormal embryonic neuroepithelium morphology ( J:87149 )

• by E10.5, the neuroepithelium in the dorsal forebrain was noticeably undulating

cellular

increased neuron apoptosis ( J:87149 )

• TUNEL staining of E14.5 embryonic brain sections suggest that increased cell death may contribute to the loss of mature neurons

abnormal neuron differentiation ( J:87149 )

• several experiments indicate that neural progenitor cell proliferation increased drastically in the mutant region

• starting from E10.5, Nestin-positive progenitor cells in the mutant showed very little radial organization

• mutant neural progenitor cells were organized into multiple clusters of neurogenic foci across the cortex and did not migrate to the outer layer of the cortex

Genotype
MGI:2451225

cn4

• Allelic Composition: Numb^tm1Ynj/Numb^tm1Ynj; Numbl^tm1Wmz/Numbl^tm1Wmz; Tg(Nes-cre)1Wmz/0
• Genetic Background: involves: 129X1/SvJ

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:79917 )

• embyros die around E12.5

growth/size/body

decreased embryo size ( J:79917 )

• embryos are 80%-90% the size of wild-type littermates

nervous system

abnormal neural tube morphology ( J:79917 )

• thinned neural tube from the most rostral telencephalon to caudal spinal cord, including optic discs

abnormal embryonic neuroepithelium morphology ( J:79917 )

• frequent buckling of the surface

decreased embryonic neuroepithelium thickness ( J:79917 )

• the neuroepithelium is only one-quarter to one-half the thickness of that in control littermates

decreased neuronal precursor cell number ( J:79917 )

• severe neural progenitor cell loss

embryo

decreased embryo size ( J:79917 )

• embryos are 80%-90% the size of wild-type littermates

abnormal neural tube morphology ( J:79917 )

• thinned neural tube from the most rostral telencephalon to caudal spinal cord, including optic discs

abnormal embryonic neuroepithelium morphology ( J:79917 )

• frequent buckling of the surface

decreased embryonic neuroepithelium thickness ( J:79917 )

• the neuroepithelium is only one-quarter to one-half the thickness of that in control littermates

Genotype
MGI:2451227

cn5

• Allelic Composition: Numb^tm1Ynj/Numb^tm1Ynj; Tg(Nes-cre)1Wmz/0
• Genetic Background: involves: 129X1/SvJ

normal phenotype

no abnormal phenotype detected ( J:79917 )

Genotype
MGI:3765970

cn6

• Allelic Composition: Numb^tm1Ynj/Numb^tm1Ynj; Numbl^tm1Wmz/Numbl^tm1Wmz; Tg(Nes-cre/Esr1*)4Ynj/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6

growth/size/body

postnatal growth retardation ( J:127227 )

• by P14 with tamoxifen induction at P0, pups show growth retardation

nervous system

increased neuron apoptosis ( J:127227 )

• at P7, many striato-cortical junction cells are apoptotic

abnormal lateral ventricle morphology ( J:127227 )

• with tamoxifen induction at P0, by P14 induced animals show structural abnormalities along the lateral ventricle wall linings whereas uninduced animals do not

enlarged lateral ventricles ( J:127227 )

• induced animals show consistent lateral ventricle enlargement by P7 compared to uninduced controls where slight enlargement is occasionally observed; by P14, enlargement is severe

• by 6 weeks of age, enlargement is significantly reduced

abnormal olfactory bulb morphology ( J:127227 )

• at P14, induced mutants display smaller olfactory bulbs with fewer interneurons, compared to uninduced controls with comparable brain size

abnormal rostral migratory stream morphology ( J:127227 )

• at P14, the rostral migratory stream (RMS) of mutants contains fewer neuroblasts than controls

• in adult induced mutants (6 weeks old), there is recovery of neuroblast numbers in RMS into the olfactory bulb

abnormal postnatal subventricular zone morphology ( J:127227 )

• at P14, the rostral migratory stream (RMS) of mutants contains fewer neuroblasts than controls

• in adult induced mutants (6 weeks old), there is recovery of neuroblast numbers in RMS into the olfactory bulb

abnormal ependyma morphology ( J:127227 )

• at P7, induced animals show occasional gaps in the ependymal lining rather than a continuous lining; by P14, the gaps progress to ependymal detachment

• at P7, occasional defects in lateral wall integrity are seen compared to uninduced controls, but by P14, defects are severe with many areas having lost the ependyma and underlying subventricular zone (SVZ) niche

• at P7, induced mutants show a poorly formed ependyma with pseudocolumnar cells instead of a flat epithelial sheath; at P14, some ependymal cells detach and remaining cells form short, defective borders with separation between cells

• by 6 weeks of age, ventricular lining is composed of a multi-layered stratified epithelium instead of a single-cell layer seen in controls; epithelial barrier is composed of mixture of astrocytes and few ependymal cells, intermixed with scar tissue

cellular

increased neuron apoptosis ( J:127227 )

• at P7, many striato-cortical junction cells are apoptotic