All Phenotypes Bptf<tm1.1Cwu> MGI Mouse

mortality/aging ( J:334252 )

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

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

abnormal head shape ( J:334252 )

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

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

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

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

behavior/neurological phenotype ( J:334252 )

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

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

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

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

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