ArticlePloS one2014
A novel mouse Fgfr2 mutant, hobbyhorse (hob), exhibits complete XY gonadal sex reversal.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Postnatal Ovarian Transdifferentiation in the Absence of Estrogen Receptor Signaling Is Dependent on Genetic Background.Endocrinology · 2024Article
- Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review.Frontiers in endocrinology · 2024Review
- Partial male-to-female reprogramming of mouse fetal testis by Sertoli cell ablation.Development (Cambridge, England) · 2023Article
- Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects.Nature communications · 2023Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Mammalian X-chromosome inactivation: proposed role in suppression of the male programme in genetic females.Journal of genetics · 2022Article
- Testis Determination Requires a Specific FGFR2 Isoform to Repress FOXL2.Endocrinology · 2017Article
- Protein purification and analysis: next generation Western blotting techniques.Expert review of proteomics · 2017Review
- The expression profiles of fibroblast growth factor 9 and its receptors in developing mice testes.Organogenesis · 2016Article
- The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.Disease models & mechanisms · 2015Article
- Understanding sex determination in the mouse: genetics, epigenetics and the story of mutual antagonisms.Journal of genetics · 2015Review
- FGFR2 mutation in 46,XY sex reversal with craniosynostosis.Human molecular genetics · 2015Article
- Vascular endothelial growth factor A: just one of multiple mechanisms for sex-specific vascular development within the testis?The Journal of endocrinology · 2015Review
- Capillary nano-immunoassays: advancing quantitative proteomics analysis, biomarker assessment, and molecular diagnostics.Journal of translational medicine · 2015Review
- Cell fate commitment during mammalian sex determination.Current opinion in genetics & development · 2015Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The secreted molecule fibroblast growth factor 9 (FGF9) plays a critical role in testis determination in the mouse. In embryonic gonadal somatic cells it is required for maintenance of SOX9 expression, a key determinant of Sertoli cell fate. Conditional gene targeting studies have identified FGFR2 as the main gonadal receptor for FGF9 during sex determination. However, such studies can be complicated by inefficient and variable deletion of floxed alleles, depending on the choice of Cre deleter strain. Here, we report a novel, constitutive allele of Fgfr2, hobbyhorse (hob), which was identified in an ENU-based forward genetic screen for novel testis-determining loci. Fgr2hob is caused by a C to T mutation in the invariant exon 7, resulting in a polypeptide with a mis-sense mutation at position 263 (Pro263Ser) in the third extracellular immunoglobulin-like domain of FGFR2. Mutant homozygous embryos show severe limb and lung defects and, when on the sensitised C57BL/6J (B6) genetic background, undergo complete XY gonadal sex reversal associated with failure to maintain expression of Sox9. Genetic crosses employing a null mutant of Fgfr2 suggest that Fgr2hob is a hypomorphic allele, affecting both the FGFR2b and FGFR2c splice isoforms of the receptor. We exploited the consistent phenotype of this constitutive mutant by analysing MAPK signalling at the sex-determining stage of gonad development, but no significant abnormalities in mutant embryos were detected.
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