Neither could we detect PTPRT protein in liver or muscle. Our data indicate that PTPRT does not directly modulate insulin sensitivity in peripheral tissues. Instead, PTPRT may indirectly impact peripheral insulin resistance through affecting the nervous Gambogic-acid system control of energy homeostasis. Fibroblast growth factorsfunction in numerous processes throughout 
embryonic development, such as the induction and patterning of germ cell layers, body axis formation and organogenesis. Out of 22 human and mouse FGFs, 18 bind to a distinct set of cell-surface FGF receptorsto initiate intracellular signalling that results in cellular responses, including cell proliferation and differentiation. Our understanding of the physiological roles of FGF ligands and their receptors has been helped enormously by the study of mouse knockouts. Ranging from early embryonic lethality to adult metabolic abnormalities, these mutant phenotypes reveal the breadth of impact of FGF signalling. Testis determination in the embryo normally requires the Ylinked gene Sry to initiate the commitment of somatic cells in the developing bipotential gonad to the Sertoli cell fate. SRY effects this commitment through its positive effects on the expression of Sox9, a gene that is itself necessary and sufficient for testis development. The analysis of mice lacking FGF9 first revealed a role for this signalling pathway in testis determination. Fgf9-deficient animals die around birth due to severe lung hypoplasia and, on a mixed genetic background, XY embryos exhibit a range of gonadal abnormalities ranging from testicular hypoplasia to complete sex reversal. On the C57BL/6Jbackground, which is sensitised to disruptions to testis determination, XY Fgf9-deficient embryos consistently exhibit gonadal sex reversal, indicating that some of the earliest processes in testis determination are disrupted by the absence of FGF9. Subsequent studies revealed an important role for FGF9 in maintaining high levels of Sox9 expression in the developing XY gonad, mediated at least partly by its inhibitory effects on ovarydetermining genes such as Wnt4. It has also been proposed that the rapid diffusion of secreted FGF9 along the long, thin gonad at around 11.5 dpc prevents any appreciable delay in the gonadal poles receiving the masculinising signal begun by expression of SRY at the centre of the gonad. Any such delay may result in ovotestis or ovary Ursolic-acid development in an XY embryo due to the restricted time window that is thought to define the competence of cells to respond to SRY and its downstream effectors. FGF9 acts as a paracrine FGF, mediating its effects locally by binding to and activating one of four tyrosine kinase FGFRs, using heparin sulphate proteoglycancofactor-association as a means of regulating ligand distribution and receptor binding. Loss-of-function genetic studies have identified FGFR2 as the likely receptor for embryonic gonadal FGF9. Embryos lacking FGFR2 die mid-gestation, at around 10.5 dpc, precluding a study of the effects of this loss on testis determination. Conditional gene targeting revealed partial XY gonadal sex reversal when Fgfr2 deletion was restricted temporally, from around 10.5 dpc onwards, or spatially, to gonadal somatic cells. Here we report the identification, in a mouse forward genetic screen, of a novel sex-reversing mutant allele of Fgfr2. Previous studies of Fgfr2 function in testis determination have relied on conditional gene targeting.