PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Forkhead Box Protein L2”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

61 records · Page 4Linked to original sources
PubMed2005

A novel mutation in the FOXL2 gene in a Chinese family with blepharophimosis, ptosis, and epicanthus inversus syndrome.

OBJECTIVE: To screen mutations in the forkhead transcriptional factor 2 gene (FOXL2) in six Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome(BPES). METHODS: PCR amplification and direct sequencing of the FOXL2 coding region in genomic DNA were performed in affected patients and 80 healthy controls. BLAST analysis of the sequence was made on Internet. RESULTS: A novel 951-953(delC) was found in the two affected patients of a Chinese family with BPES. No mutations were found in the healthy controls. The 951-953(delC) may cause a frameshift mutation after codon 238 that exists downstream of the forkhead domain, resulting in the production of truncated proteins. CONCLUSION: These findings indicated that the 951-953(delC) deletion mutation in the two patients resulted in truncated proteins and hence led to their BPES. To the authors' knowledge, the 951-953(delC) in FOXL2 has not been previously reported.

Amino Acid Sequence↗
PubMed2005

Premature ovarian failure and forkhead transcription factor FOXL2: blepharophimosis-ptosis-epicanthus inversus syndrome and ovarian dysfunction.

Recently the molecular basis of the blepharophimosis-ptosis-epicanthus inversus-syndrome (BPES), an autosomal dominant developmental disorder of the eyelids and ovary, was elucidated. This syndromic form of premature ovarian failure (POF) is caused by mutations in the gene encoding the forkhead transcription factor FOXL2. In this manuscript we review the clinical features of BPES, its molecular basis, the structural and functional characteristics of the FOXL2 gene and protein, and known animal models.

Animals↗
PubMed2006

[Mutation analysis of FOXL2 in Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome].

OBJECTIVE: To identify the genetic mutation in two Chinese families and 6 sporadic patients with belpharophimosis-ptosis-epicanthus inversus syndrome (BPES). METHODS: Polymorphisms of 5 satellite markers on 3q were analyzed and linkage analysis was performed using linkage software (MLINK) in all cases of two families. FOXL2 gene fragments were amplified by PCR and mutation was determined by sequencing DNA fragments in all patients. RESULTS: The BPES locus in the pedigrees was mapped to 3q23, a 9.88 cM interval between markers D3S3696 and D3S1744. The maximum lod scores were 2.11 (theta = 0.00) at D3S1549 and D3S3586 and 1.51 (theta = 0.00) at D3S1764. By direct sequencing FOXL2 gene, two sporadic cases had a 30-bp in frame duplication 909 - 938 dup 30 and one sporadic case showed a nucleotide insertion 1041 - 1042 ins C. However, it was unable to find any causal mutation of FOXL2 in two families with BPES. CONCLUSIONS: The gene responsible for BPES in two Chinese families was linked to D3S1549, D3S3586 and D3S1764. This is the first reported mutations of FOXL2 (909 - 938 dup 30 and 1041 - 1042 ins C) in Chinese sporadic cases. One of the mutations, in-frame 30-bp duplication (909 - 938 dup 30), is one of the most common mutation hotspots in the coding region of FOXL2. In BPES families without FOXL2 mutation, it cannot be excluded that the disorder is caused by a position effect in the surrounding region of FOXL2 gene or by other genes located at 3q23.

Asian People↗
PubMed2026

Regulation of murine follicle-stimulating hormone β subunit transcription by newly identified enhancers.

Activin-class ligands of the transforming growth factor β family induce follicle-stimulating hormone (FSH) production by pituitary gonadotrope cells in mice via the actions of the transcription factors SMAD3, SMAD4, and FOXL2, which bind to cis-elements in the FSHβ subunit (Fshb) promoter. An enhancer region for murine Fshb transcription was identified in vitro. However, deletion of the region using CRISPR-Cas9 did not affect FSH synthesis or secretion in mice. Using single-nucleus ATAC-seq of whole murine pituitaries, we identified 3 additional open chromatin regions upstream of Fshb exclusively in gonadotropes. These regions, as well as the Fshb gene, were fully or partially closed in gonadotropes of FSH-deficient mice with genetically or pharmacologically inactivated activin type II receptors. The initially characterized enhancer region did not significantly alter basal or activin-stimulated murine Fshb promoter-reporter activity in homologous LβT2 cells. In contrast, the other 3 open chromatin regions enhanced basal and activin A-stimulated Fshb promoter-reporter activity in LβT2 cells, with the 2 most distal showing the greatest effects. These 2 regions were open, exhibited enrichment of the enhancer mark H3K27ac, and were bound by SMAD2/3 and FOXL2 in response to activin A in LβT2 cells. The most distal enhancer exhibited strong FOXL2 and weak SMAD4 binding in gel shift assays. SMAD4, but not FOXL2, directly bound the other distal enhancer. Mutation of defined FOXL2 and SMAD4 cis-elements diminished enhancer activity in reporter assays in LβT2 cells. Collectively, the data indicate that there may be as many as 4 activin-sensitive enhancers upstream of murine Fshb.

Animals↗
PubMed2005

Follicular cells acquire sertoli cell characteristics after oocyte loss.

Although it has been suggested that in mammals the loss of female germ cells may induce the masculinization of the ovarian compartment, there has been as yet no conclusive demonstration. To directly address that question, the present study has been designed to determine the fate of follicular cells after oocyte loss. Using gamma-irradiation to selectively deplete oocytes in nongrowing follicles in female rats, we show that follicular cells in oocyte-depleted follicles survive, proliferate, and subsequently acquire morphological characteristics of Sertoli cells: elongated cytoplasm, basal location of the nucleus, and specific Sertoli cell junctions, the ectoplasmic specializations. These Sertoli-like cells express, however, the female-specific marker FOXL2 (Forkhead L2) but not the male sex-specific marker SOX-9 (Sry-type high-mobility-group box transcription factor-9) underlying the maintenance of molecular characteristics of granulosa cells. Before transdifferentiating into Sertoli-like cells, follicular cells of oocyte-depleted follicles initiate the expression of anti-Mullerian hormone and inhibin alpha-subunit that are typically synthesized by granulosa cells from the onset of follicular growth. Experimental modifications of the endocrine balance of the irradiated females show that there is a close relationship between plasma FSH levels and the occurrence of Sertoli-like cells. In addition to providing experimental evidence for the crucial role of the oocyte in granulosa cell phenotype maintenance, these results emphasize that the transdifferentiation of granulosa cells into Sertoli cells occurs in a multistep fashion, requiring the maturation of granulosa cells and depending on the endocrine milieu.

Animals↗
PubMed2005

Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise.

To search for novel transcriptional pathways that are activated in skeletal muscle after endurance exercise, we used cDNA microarrays to measure global mRNA expression after an exhaustive bout of high-intensity cycling (approximately 75 min). Healthy, young, sedentary males performed the cycling bout, and skeletal muscle biopsies were taken from the vastus lateralis before, and at 3 and 48 h after exercise. We examined mRNA expression in individual muscle samples from four subjects using cDNA microarrays, used repeated-measures significance analysis of microarray (SAM) to determine statistically significant expression changes, and confirmed selected results using real-time RT-PCR. In total, the expression of 118 genes significantly increased 3 h postcycling and 8 decreased. At 48 h, the expression of 29 genes significantly increased and 5 decreased. Many of these are potentially important novel genes involved in exercise recovery and adaptation, including several involved in 1) metabolism and mitochondrial biogenesis (FOXO1, PPARdelta, PPARgamma, nuclear receptor binding protein 2, IL-6 receptor, ribosomal protein L2, aminolevulinate delta-synthase 2); 2) the oxidant stress response (metalothioneins 1B, 1F, 1G, 1H, 1L, 2A, 3, interferon regulatory factor 1); and 3) electrolyte transport across membranes [Na+-K+-ATPase (beta3), SERCA3, chloride channel 4]. Others include genes involved in cell stress, proteolysis, apoptosis, growth, differentiation, and transcriptional activation, as well as all three nuclear receptor subfamily 4A family members (Nur77, Nurr1, and Nor1). This study is the first to characterize global mRNA expression during recovery from endurance exercise, and the results provide potential insight into 1) the transcriptional contributions to homeostatic recovery in human skeletal muscle after endurance exercise, and 2) the transcriptional contributions from a single bout of endurance exercise to the adaptive processes that occur after a period of endurance exercise training.

Adult↗