Phenotypes associated with this allele

• Allele Symbol: Bptf^tm1.1Cwu
• Allele Name: targeted mutation 1.1, Carl Wu
• Allele ID: MGI:3841297
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Bptf^tm1.1Cwu/Bptf^tm1.1Cwu Foxg1^tm1(cre)Skm/?	involves: 129P2/OlaHsd-Hprt^b-m3 * 129S1/Sv-Oca2^+ Tyr^+ Kitl^+	MGI:6763182
cn2	Bptf^tm1.1Cwu/Bptf^tm1.1Cwu Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:7518724

Genotype
MGI:6763182

cn1

• Allelic Composition: Bptf^tm1.1Cwu/Bptf^tm1.1Cwu; Foxg1^tm1(cre)Skm/?
• Genetic Background: involves: 129P2/OlaHsd-Hprt^b-m3 * 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺

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

mortality/aging

perinatal lethality, complete penetrance ( J:217534 )

taste/olfaction

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

nervous system

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

growth/size/body

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

respiratory system

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

craniofacial

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

Genotype
MGI:7518724

cn2

• Allelic Composition: Bptf^tm1.1Cwu/Bptf^tm1.1Cwu; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * C57BL/6

mortality/aging

mortality/aging ( J:334252 )

N • mice are born in normal Mendelian ratios and survive to adulthood

growth/size/body

abnormal head shape ( J:334252 )

• mice exhibit an oddly shaped head at 9 months of age

decreased body weight ( J:334252 )

• mice show a significant reduction in body weight by P2; growth differences are maintained as mice grow older and are readily obvious by P10

• however, body weight is relatively normal at birth

craniofacial

abnormal head shape ( J:334252 )

• mice exhibit an oddly shaped head at 9 months of age

nervous system

increased neuron apoptosis ( J:334252 )

• at E15.5, but not at E13.5, mice show a 10-fold increase in the % of cleaved caspase 3-positive (CC3+) apoptotic cells within the intermediate zone (IZ) and cortical plate (CP) relative to control and heterozygous littermates; however, the % of apoptotic cells within the ventricular zone (VZ) is unaffected

• % of CC3+ cells remains elevated as late as P2, when it becomes accompanied by a similar 10-fold increase in Iba1+ microglia cells

abnormal neuronal precursor proliferation ( J:334252 )

• cortical progenitor cells show a 10% decrease in the fraction of cells exiting the cell cycle within a 24-h period, suggesting that cell cycle length is prolonged

• however, no blocks are noted in the cell cycle with normal cell proportions in the S- and M-phase relative to control samples

microgliosis ( J:334252 )

• at E15.5, but not at E13.5, mice exhibit more Iba1+ activated microglia within the ventricular zone (VZ) relative to control mice; however, levels of microglia within the intermediate zone (IZ) and cortical plate (CP) remain normal

• by P2, cortex shows a 10-fold increase in Iba1+ microglia cells relative to control and heterozygous samples, with a significantly higher incidence of Iba1+ CC3+ co-labeled cells

• frequency of Iba1+ cells remains significantly high at P7

decreased brain weight ( J:334252 )

• at birth (P0.5), mice show a significant reduction in brain weight resulting in a decreased brain weight to body weight ratio

decreased forebrain size ( J:334252 )

• at P12, mice show a massive reduction in forebrain size relative to control and heterozygous littermates

forebrain hypoplasia ( J:334252 )

• at P26, gross morphology of the hypoplastic forebrain is identical to that observed at P12, suggesting a developmental phenotype that does not worsen with age

abnormal cerebral cortex morphology ( J:334252 )

• mice exhibit severe cortical hypoplasia that is present from birth

abnormal stratification in cerebral cortex ( J:334252 )

• at P2, the proportion of superficial, late-born Satb2+ neurons (upper layers IIV) is reduced by 45% with fewer Satb2+ cells present in layer V and some Satb2+ cells located below layer VI; the proportion of deep, early-born Tbr1+ neurons (layer VI) is also significantly decreased

• Ctip2 immunostaining showed both lamination and cell fate defects: the proportion of Ctip2^high neurons in layer V is reduced >90%, while the proportion of Ctip2^low cells shows a 60% reduction in layer VI along with a 2.7-fold increase in layers IIIII

• immunostaining of Foxp1 (normally expressed in layers IV and V of the cortex) showed an overall decrease in the proportion of Foxp1+ cells, with most located within layer IV

decreased neuronal precursor cell number ( J:334252 )

• at E15.5, the % of Tbr2+/Hoechst+ intermediate progenitor cells (IPCs) is slightly but significantly decreased in forebrain sections

• however, radial glia progenitor cells (RGCs) show no reduction in cell number or any blocks in cell cycle progression that alter proliferation

abnormal neuron specification ( J:334252 )

• neuron fate specification defects include layer VI and layer II-IV neurons that maintain Ctip2 protein expression inappropriately, a massive decrease in Ctip2+ and Foxp1+ layer V neurons, and misplaced Satb2+ neurons residing below layer VI that likely never complete their migration to the upper layers

immune system

microgliosis ( J:334252 )

• at E15.5, but not at E13.5, mice exhibit more Iba1+ activated microglia within the ventricular zone (VZ) relative to control mice; however, levels of microglia within the intermediate zone (IZ) and cortical plate (CP) remain normal

• by P2, cortex shows a 10-fold increase in Iba1+ microglia cells relative to control and heterozygous samples, with a significantly higher incidence of Iba1+ CC3+ co-labeled cells

• frequency of Iba1+ cells remains significantly high at P7

cellular

increased neuron apoptosis ( J:334252 )

• at E15.5, but not at E13.5, mice show a 10-fold increase in the % of cleaved caspase 3-positive (CC3+) apoptotic cells within the intermediate zone (IZ) and cortical plate (CP) relative to control and heterozygous littermates; however, the % of apoptotic cells within the ventricular zone (VZ) is unaffected

• % of CC3+ cells remains elevated as late as P2, when it becomes accompanied by a similar 10-fold increase in Iba1+ microglia cells

abnormal neuronal precursor proliferation ( J:334252 )

• cortical progenitor cells show a 10% decrease in the fraction of cells exiting the cell cycle within a 24-h period, suggesting that cell cycle length is prolonged

• however, no blocks are noted in the cell cycle with normal cell proportions in the S- and M-phase relative to control samples

hematopoietic system

microgliosis ( J:334252 )

• at E15.5, but not at E13.5, mice exhibit more Iba1+ activated microglia within the ventricular zone (VZ) relative to control mice; however, levels of microglia within the intermediate zone (IZ) and cortical plate (CP) remain normal

• by P2, cortex shows a 10-fold increase in Iba1+ microglia cells relative to control and heterozygous samples, with a significantly higher incidence of Iba1+ CC3+ co-labeled cells

• frequency of Iba1+ cells remains significantly high at P7

behavior/neurological

behavior/neurological phenotype ( J:334252 )

N • adult mice show no differences in home cage behavior relative to control littermates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurodevelopmental disorder with dysmorphic facies and distal limb anomalies		DOID:0070514	OMIM:617755	J:334252