This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, studies have found rare mutations in the FOXG1 gene that are associated with FOXG1 syndrome (Kortm et al., 2011) and Rett's syndrome (quite a bit of phenotypic overlap exists between these two syndromes) as well as West syndrome.
Molecular Function
Transcription factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon.
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References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum h...
FoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes
FoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Foxg1-Cre knock-in/knock-out mice express Cre recombinase from the endogenous Foxg1 locus.
Allele Type: Knockout
Strain of Origin: 129P2/OlaHsd-Hprt^b-m3
Genetic Background: C57BL/6J
ES Cell Line: HM-1
Mutant ES Cell Line: Model Source: Jackson Laboratory
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
Foxg1 low models were generated by crossing male nex-cre4; dlx-cre animals with female foxg1-c/c; r26-cag-frted stop-egfp homozygous animals (rce:frt, jackson laboratories stock #10812). upon cre-mediated recombination, the conditional floxed-foxg1 allele is converted into a flpe knock-in allele, and thus the recombination efficiency in each animal can be evaluated by egfp expression from the flp-dependent egfp reporter rce:frt. the conditional floxed ready foxg1 allele has loxp sites inserted to flank the foxg1 coding sequence. this model preserves foxg1 expression in neural progenitors and glial cells and selectively deletes foxg1 in postmitotic glutamatergic (nex-cre) and gabaergic (dlx-cre) neurons of the forebrain.
Allele Type: Conditional knockout
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Model Source: Miyoshi et al, 2010; Miyoshi, et al, 2012, 22726835
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
A null mutation of foxg1 was generated by replacing 2.3kb of coding sequence with a lacz and neomycin cassette
Allele Type: Knockout
Strain of Origin: 129S1/Sv-Oca2+ Tyr+ Kitl+
Genetic Background: C57BL/6J
ES Cell Line: CJ7 (ES Cell)
Mutant ES Cell Line: CJ7 (ES Cell)
Model Source: Xuan et al, 1995; 7605629
Model Type:
RESCUE-Transplantation
Model Genotype:
Heterozygous
Mutation:
Augmentation of gabaergic systems during the juvenile critical period, 1-2 weeks, was accompilshed in the foxg1 het model by gabaergic cell precursor transplantation into the mpfc. dissociated egfp-labeled gabaergic cell precursors (dlx-cre; rce:loxp59,60) from the e13.5 medial ganglionic eminences (mge) that are wild type for foxg1, were bilaterally transplanted into the postnatal 1 week medial prefrontal cortices, and e/i ratios analyzed at 2 weeks. miniature frequencies of mpfc layer 2/3 cells were analyzed one week after the transplantation.
Allele Type: Knockout
Strain of Origin: 129S1/Sv-Oca2+ Tyr+ Kitl+
Genetic Background: C57BL/6J
ES Cell Line: Mutant ES Cell Line: Model Source: 7605629
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
Foxg1 glu-low models were generated by crossing male nex-cre4; animals with female foxg1-c/c; r26-cag-frted stop-egfp homozygous animals (rce:frt, jackson laboratories stock #10812). upon cre-mediated recombination, the conditional floxed-foxg1 allele is converted into a flpe knock-in allele, and thus the recombination efficiency in each animal can be evaluated by egfp expression from the flp-dependent egfp reporter rce:frt. the conditional floxed ready foxg1 allele has loxp sites inserted to flank the foxg1 coding sequence. this model preserves foxg1 expression in neural progenitors and glial cells and selectively deletes foxg1 in postmitotic glutamatergic (nex-cre).
Allele Type: Conditional knockout
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Model Source: Miyoshi et al, 2010; Miyoshi, et al, 2012, 22726835
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
Foxg1 gaba- low models were generated by crossing male dlx-cre animals with female foxg1-c/c; r26-cag-frted stop-egfp homozygous animals (rce:frt, jackson laboratories stock #10812). upon cre-mediated recombination, the conditional floxed-foxg1 allele is converted into a flpe knock-in allele, and thus the recombination efficiency in each animal can be evaluated by egfp expression from the flp-dependent egfp reporter rce:frt. the conditional floxed ready foxg1 allele has loxp sites inserted to flank the foxg1 coding sequence. this model preserves foxg1 expression in neural progenitors and glial cells and selectively deletes foxg1 in postmitotic gabaergic (dlx-cre) neurons of the forebrain.
Allele Type: Conditional knockout
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Model Source: Miyoshi et al, 2010; Miyoshi, et al, 2012, 22726835
Model Type:
Genetic GOF
Model Genotype:
Heterozygous
Mutation:
Foxg1 high models were generated by crossing male nex-cre; dlx-cre animals to female r26-stop-tta homozygous (conditional transactivator; jackson laboratories stock #008600); tre-foxg1 homozygous animals. tre-foxg1, a foxg1 expression allele contains an ires-lacz cassette downstream of the foxg1 coding sequence so that foxg1 gof population can be visualized based on x-gal staining. since foxg1 gain-of-function can disrupt migration of pyramidal neurons, foxg1 expression is augmented during the early postnatal period after most neuronal migration is complete (~1st postnatal week; p7). to delay foxg1 augmentation until after postnatal 1 week, a doxycycline-containing diet (200 ppm, #1810413 test diet) was provided to the pregnant females from the date of the observed plug until postnatal day 7.
Allele Type: Conditional knockout
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Model Source: Miyoshi et al, 2010; Miyoshi, et al, 2012, 22726835
Model Type:
Genetic LOF
Model Genotype:
Homozygous
Mutation:
A null mutation of foxg1 was generated by replacing 2.3kb of coding sequence with a lacz and neomycin cassette. heterozygotes are indistinguishable from wild-type littermates, except by the expression of beta-gal.
Allele Type: Knockout
Strain of Origin: 129S1/Sv-Oca2+ Tyr+ Kitl+
Genetic Background: C57BL/6J
ES Cell Line: CJ7 (ES Cell)
Mutant ES Cell Line: CJ7 (ES Cell)
Model Source: Xuan et al, 1995; 7605629
Description: Foxg1 heterozygous mice displayed lower reach scores compared to wildtype mice, with no sex differences among mutant mice; reach scores of Foxg1 heterozygous mice improved much less with training and reached a plateau below 2; latency to reach was also greater in mutant mice.
Description: Abnormal brain development indicated by abnormal representation of neurons in cortex
Exp Paradigm: In situ hybridization and immunocytochemistry using markers against specific layers in cortex
Description: Decreased dimension of cerebral hemisphere demonstrated by decreased medio-lateral and midline anterior-posterior length
Exp Paradigm: Magnetic resonance microscopy (mrm) of fixed tissue
Description: Decreased cortical thickness in supragranular (i-iii), granular (iv) and infragranular (v-vi) layers along with decreased total number of cells
Exp Paradigm: Photomicrographic analysis of co stained coronal sections
Description: Decreased thalamic volume along with reduction in total number of cells in ventrobasal complex of thalamus
Exp Paradigm: Magnetic resonance microscopy of sagittal sections; cell counting of nissl-stained section
Description: Decreased volume of posencephalon reflecting alterations in volume of telencephalic structures
Exp Paradigm: Magnetic resonance microscopy of intact male brains
Description: Decreased area of cortical sheet, barrel field size and individual barrels with a pronounced rostral effect
Exp Paradigm: Immunohistochemistry
Description: On the training day, there was no genotype difference in activity or percent freezing during the baseline period; Foxg1 heterozygous mice showed an increased response to the shocks average motion during the shocks.
Description: Foxg1 heterozygous mice spent less time in the anxiety-provoking center of the open field than wildtype mice; females spent more time in the center of the open field than males.
Description: On the training day, Foxg1 heterozygous mice showed reduced freezing between the two tone-shock interval, indicating reduced acquisition of fear.
Description: Altered e/i mepsc to mipsc frequency but not amplitude ratio within the medial prefrontal cortex; mepsc and mipsc measured in layer 2/3 pyramidal neurons of the medial prefrontal cortex (prelimbic and infralimbic)
Description: Foxg1 protein levels within the medial prefrontal cortex at postnatal 2 and 6 weeks by western blotting reduced to half; foxg1 protein levels change 2 days upon addition or removal of the doxycycline-containing diet
Description: Decreased e/i mepsc to mipsc frequency but not amplitude ratio within the medial prefrontal cortex; mepsc and mipsc measured in layer 2/3 pyramidal neurons of the medial prefrontal cortex (prelimbic and infralimbic); no change in the barrel cortex
Description: Peak of gamma-band frequency of eeg in awake free-moving state with the electrodes aligned nearby the medial prefrontal cortex was reduced and shifted to a lower frequency range; overall reduction in high-gamma frequency power (55â??80 hz)
Description: Foxg1 protein levels within the medial prefrontal cortex at postnatal 2 and 6 weeks by western blotting reduced to half; foxg1 protein levels change 2 days upon addition or removal of the doxycycline-containing diet
Description: Foxg1 protein levels within the medial prefrontal cortex at postnatal 2 and 6 weeks by western blotting reduced to half; foxg1 protein levels change 2 days upon addition or removal of the doxycycline-containing diet
Description: Animals exhibit social approach deficits only when foxg1 is augmented in both glu+gaba lineages simultaneously; milder phenotype than pan het and gg-low
Description: Animals exhibit social novelty deficits only when foxg1 is augmented in both glu+gaba lineages simultaneously; milder than pan het phenotype
Description: Foxg1 protein levels within the medial prefrontal cortex at postnatal 2 weeks increased; increase of foxg1 protein is suppressed by continuous feeding of doxycycline; foxg1 protein levels change 2 days upon addition or removal of the doxycycline-containing diet
Description: Abnormal morphogenesis of the telencephalon, dorsal telencephalic vesicles of the are positioned more ventrally and closer to the level of the eyes; dorsal telencephalon is reduced in size, the ventral telencephalon is almost completely absent; mutant tissue that expressed the beta-gal is negative for the expression of the dorsal telencephalic markers, emx2 and pax6
Description: Almost all of the telencephalic neuroepithelium at e12.5 expressed the dorsal markers emx2, neither ventral marker, dix2 and dix 1 were expressed in the telencephalic neuroepithelium; dorsal telencephalic neuroepithelial cells also differentiate prematurely; early withdrawal of telencephalic neuroepithelial cells from the cell cycle and in the premature onset of neuronal differentiation.
Description: Reduced proliferation of telencephalic neuroepithelial cells , no significant differences were observed in the brdu labeling patterns of mutant and wild-type embryos at e9.5; decreased brdu-labeled cells in both dorsal and ventral regions of the mutant telencephalon at e10.5, early depletion of neural progenitor population; absence of ventral telencephaion primarily due to the failure of precursor cells in this region to continue proliferating actively after e9.5
