Disease relevance of Gfra2

• In the Gfra2-/- mice, density of substance P-containing myenteric ganglion cells and nerve bundles in the myenteric ganglion cell layer was significantly reduced, and transit of test material through small intestine was 25% slower compared to wild-type mice [1].

High impact information on Gfra2

• Here we describe the identification and tissue distribution of a GPI-linked protein (designated NTNR-alpha) that is structurally related to GDNFR-alpha [2].
• Retarded growth of the Gfra2-/- mice was accompanied by reduced fat mass and elevated basal metabolic rate [1].
• These results provide evidence that signaling through GFR alpha 2 is involved in mechanisms regulating the development and persistence of kindling epilepsy [3].
• Studied by in situ hybridisation, GDNFR-beta mRNA shows in E17 rat embryo different distribution to that of GDNFR-alpha mRNA, especially, in adrenal gland, kidney and gut [4].
• Cloning strategies were used to identify a gene termed glial cell line-derived neurotrophic factor receptor-beta (GDNFR-beta) related to GDNFR-alpha [5].

Biological context of Gfra2

• In accordance with the phenotype of the mutant motoneurons observed in culture we found the loss of distinct groups of motoneurons, identified by several markers, in the Gfra1(-/-) spinal cords but no gross defects in the Gfra2(-/-) mutant [6].
• Two candidate genes, GFR alpha 2 and GnRH, that were previously mapped to that region and the functions of which in spermatogenesis are well established were not altered in DMS [7].

Anatomical context of Gfra2

• Gfra1 mRNA was expressed at E12 but not in newborn cranial parasympathetic ganglia, while Gfra2 mRNA and protein were strongly expressed in newborn and adult cranial parasympathetic neurons and their projections, respectively [8].
• GDNFR-beta mRNA was more widely expressed in the developing and adult CNS, including cerebral cortex, cerebellum, thalamus, zona incerta, hypothalamus, brainstem, and spinal cord, and in subpopulations of sensory neurons and developing peripheral nerves [5].
• Identification of GFR alpha-2 isoforms in myenteric plexus of postnatal and adult rat intestine [9].
• Quantitative PCR showed that GFR alpha-2 is by far the dominant ligand binding chain in T cells, B cells, and monocytes [10].

Other interactions of Gfra2

• Moreover, adult Gfra2(-/-) mice showed reduced cholinergic innervation by 40% in their ventricles and by 60% in the ventricular conduction system [11].
• NTN utilizes a receptor complex system that consists of Ret and another GPI-linked receptor, NTNR alpha [12].
• At the protein level, mouse GFR alpha-3 is 35% identical to mouse GDNFR alpha and 36% identical to mouse NTNR alpha [12].
• Neurturin and GDNFR-beta were present in developing sensory organs [5].
• Three mRNAs, Gfra2, TrkA, and TrkC, were differentially expressed [13].

Analytical, diagnostic and therapeutic context of Gfra2

• By whole-mount in situ hybridization on embryonic mouse spinal cord, we demonstrate that whereas Ret is expressed by nearly all motoneurons, Gfra1 and Gfra2 exhibit complex and distinct patterns of expression [6].
• Quantification of mouse glial cell-line derived neurotrophic factor family receptor alpha 2 alternatively spliced isoforms by real time detection PCR using SYBR Green I [14].
• The aim of this study was therefore to identify GFR alpha-2 splice isoforms in rat tissues using reverse transcription-polymerase chain reaction (RT-PCR) and gene cloning [9].

References