Disease relevance of Foxc1

• Foxc1/Mf1 is disrupted in the mutant, congenital hydrocephalus (Foxc1/Mf1(ch)), which has multiple developmental defects [1].
• Here, we show that mouse embryos compound mutant for Foxc1 and Foxc2, two closely related Fox transcription factors, exhibit arteriovenous malformations and lack of induction of arterial markers whereas venous markers such as COUP-TFII are normally expressed, suggesting that mutant endothelial cells fail to acquire an arterial fate [2].
• Expression of the Mf1 gene in developing mouse hearts: implication in the development of human congenital heart defects [3].
• To this end, high-dose attenuated VSV-G pseudotyped equine infectious anaemia virus (EIAV) encoding beta-galactosidase under the CMV promoter was injected into the fetal circulation of immuno-competent MF1 mice [4].
• We report here that recombinant retrovirus producing cells administered into the intra-amniotic cavity of mid- to late-gestation mouse MF1 foetuses survive in the amniotic fluid and are able to engraft to a certain extent in foetal tissues [5].

Psychiatry related information on Foxc1

• The effects of the doubly labelled water technique (intraperitoneal injection, temporary food deprivation and blood sampling) on the energy expenditure, food intake and behaviour of 18 white (MF1) mice was investigated [6].

High impact information on Foxc1

• We show that a commercially available strain of outbred mice, MF1, can be treated as an ultrafine mosaic of standard inbred strains and accordingly used to dissect a known quantitative trait locus influencing anxiety [7].
• Mf1 encodes a forkhead/winged helix transcription factor expressed in many embryonic tissues, including prechondrogenic mesenchyme, periocular mesenchyme, meninges, endothelial cells, and kidney [8].
• The human Mf1 homolog FREAC3 is a candidate gene for ocular dysgenesis and glaucoma mapping to chromosome 6p25-pter, and deletions of this region are associated with multiple developmental disorders, including hydrocephaly and eye defects [8].
• We show that congenital hydrocephalus involves a point mutation in Mf1, generating a truncated protein lacking the DNA-binding domain [8].
• Mutant fetuses are retarded in growth and die at mid-gestation in a 129/Sv genetic background, whereas in a 129/Sv x C57BL/6 cross some survive until birth and even to postnatal day 20 in a 129/Sv x C57BL/6 x MF1 background [9].

Chemical compound and disease context of Foxc1

• A mouse model of Chlamydia pneumoniae pneumonitis was established in outbred MF1 mice immunosuppressed with cyclophosphamide [10].
• A single dose of 8 mg cisplatin/kg body weight administered to MF1 mice by an ip injection reduced the number of resting primary spermatocytes only [11].
• Hyperglycemia associated with the manifestation of the obese diabetic (ob/ob) syndrome in mice and the short and long term streptozotocin treatment of lean MF1 mice was accompanied by a significant decrease in erythrocyte glyoxalase 1 activity and a marked increase in the concentration of the alpha-oxoaldehyde methylglyoxal [12].

Biological context of Foxc1

• Embryos lacking either Foxc1 or Foxc2, and most compound heterozygotes, die pre- or perinatally with similar abnormal phenotypes, including defects in the axial skeleton and cardiovascular system [13].
• In support of this hypothesis, we show here that compound Foxc1; Foxc2 homozygotes die earlier and with much more severe defects than single homozygotes alone [13].
• FGF10 stimulates the growth and branching morphogenesis in cultures of wild type and Foxc1 mutant gland epithelial buds [14].
• Progression of calvarial bone development requires Foxc1 regulation of Msx2 and Alx4 [15].
• We therefore suggest that Foxc1 regulates BMP-mediated osteoprogenitor proliferation and that this regulation is required for the progression of osteogenesis beyond the initial condensations in calvarial bone development [15].

Anatomical context of Foxc1

• We show here that, depending on the genetic background, most Foxc1 homozygous mutants are born with abnormalities of the metanephric kidney, including duplex kidneys and double ureters, one of which is a hydroureter [1].
• Foxc1 is expressed in both the epithelium of the lacrimal gland and the surrounding mesenchyme [14].
• The murine Foxc1/Mf1 and Foxc2/Mfh1 genes encode closely related forkhead/winged helix transcription factors with overlapping expression in the forming somites and head mesoderm and endothelial and mesenchymal cells of the developing heart and blood vessels [13].
• In gain of function studies in the chick embryo, Foxc1 and Foxc2 negatively regulate intermediate mesoderm formation [16].
• These heterodimers appear to control: (1) the remodeling of the POM through activation of Eya2-related apoptosis; (2) the expression of Foxc1 and Pitx2, which play crucial roles in anterior eye segment development; and (3) the growth of the ventral retina [17].

Associations of Foxc1 with chemical compounds

• Thus the specific activities of (Na+ + K+)-ATPase, Ca2+-ATPase and lysophosphatidylcholine acyltransferase were several-fold enriched in MF2 compared to MF1 [18].
• Oocytes from MF1 mice responded to 8.7% ethanol and to 0.3% benzyl alcohol by a depolarization (sometimes preceded by a brief hyperpolarization) [19].
• METHODS: Mice (MF1) bearing LS174T human tumor xenografts were injected with premixed (18)F-FDG (100 MBq), (14)C-2DG (0.37 MBq), and pimonidazole hydrochloride (60 mg/kg) [20].
• Similarly, aortic relaxation to acetylcholine was significantly impaired in MF1 aortic rings compared with in C57BL/6J aortae; these differences were reversed by Tiron [21].
• N(G)-monomethyl- L -arginine induced significantly less vasoconstriction in MF1 and 129sv hearts compared with C57BL/6J [21].

Other interactions of Foxc1

• This study demonstrates that Foxc1 mediates the BMP signaling required for lacrimal gland development [14].
• We also show that BMP-induced expression of Msx2 and Alx4 requires Foxc1 [15].
• We have shown previously that the winged helix transcription factor Foxc1, which is necessary for calvarial bone development, is required for the Bmp regulation of Msx2 [22].
• We also localized a second member of this gene family ( Hfh1 ), a candidate for other developmental defects, approximately 470 kb proximal to Mf1 [23].
• MF-1 RNA is present in non-notochordal mesoderm, and in neural-crest-derived head mesenchyme, while MF-2 transcripts are found in the sclerotomes of the somites and in head mesenchyme, including that from neural crest [24].

Analytical, diagnostic and therapeutic context of Foxc1

• In order to evaluate its contribution to normal heart septation and valve formation, expression of the mouse homologue Mf1 in embryonic hearts was analyzed by in situ hybridization [3].
• Electron microscopy combined with a quantitative analysis was used to study the virus-like particles appearing in oocytes and preimplantation embryos of nine mouse strains: inbred AKR, NZB, BALB/c, and C3H/He; randomized Swiss; inbred DDK; noninbred Peru; and randombred Q and MF1 [25].
• Subcutaneous injection of Rama 900 into thymectomised rats or MF1 nu/nu mice yielded fewer tumours, most of which regressed [26].
• Northern blot hybridisation reveals that the most abundant MIP mRNA transcript in the adult CAT lens is truncated when compared to that in the adult MF1 lens [27].
• BALB/c and MF1 mice were examined; as well as transgenic mice with the gene defect of cystic fibrosis (CF) in the airways as an animal model for this disease [28].

References