Disease relevance of Ptch2

• In many cases, medulloblastoma arising from perturbations of Ptch1 function leads to a concomitant up-regulation of a highly similar gene, Patched2 (Ptch2) [1].
• In addition, all of the reported Hirschsprung's disease point mutations in the RETtk (S289P, R421Q, and R496G) inactivate RET/ptc2 in our assay, confirming that these are loss of function mutations [2].

High impact information on Ptch2

• Ptch2, a second mouse Patched gene is co-expressed with Sonic hedgehog [3].
• Despite the dynamic expression of Ptc2 during embryogenesis, Ptc2(tm1/tm1) mice are viable, fertile, and apparently normal [4].
• While functional compensation by Ptc1 might account for the lack of a strong mutant phenotype in Ptc2-deficient mice, our results suggest that normal Ptc2 function is required for adult skin homeostasis [4].
• Most notably, Ptc2 is expressed in an overlapping pattern with Shh in the epidermal compartment of developing hair follicles and is highly expressed in the developing limb bud, cerebellum, and testis [4].
• As increased expression of Ptch2 is associated with medulloblastoma and other tumors, we investigated the role of Ptch2 in tumor suppression by generating Ptch2-deficient mice [1].

Biological context of Ptch2

• Overlapping and non-overlapping Ptch2 expression with Shh during mouse embryogenesis [5].
• Single-strand conformation polymorphism analysis was used to map mouse Ptch2 to chromosome 4 between the microsatellite markers D4Mit20 and D4Mit334 [6].
• We determined the genomic structure of the mouse Ptch2 gene and show that Ptch2 is composed of 22 exons spanning approximately 18 kb of genomic DNA [6].
• Both dhh and ptc2 mRNA levels were down-regulated during the degenerative phase postinjury in WT mice, while levels rose again during the phase of nerve regeneration [7].
• Tyrosines outside the kinase core and dimerization are required for the mitogenic activity of RET/ptc2 [2].

Anatomical context of Ptch2

• In the developing tooth, hair and whisker, Shh and Ptch2 are co-expressed in the epithelium while Ptch is strongly expressed in the mesenchymal cells [5].
• By immunohistochemistry, Ptc2 protein was seen on unmyelinated nerve fibers [7].
• Using RT-PCR in purified cultures of mouse Schwann cells and fibroblasts, we found ptc2 mRNA in Schwann cells, and at much lower levels, in fibroblasts [7].
• These results suggest that the Dhh-Ptc2 signaling pathway may be involved in the maintenance of adult nerves and may be one of the factors that directly or indirectly determines the response of peripheral nerves to injury [7].
• The mRNAs encoding key effectors of Hh signalling, Ptc2, Smo, and Fu, are also most apparent in spermatogonia, spermatocytes, and to a lower extent in round spermatids [8].

Associations of Ptch2 with chemical compounds

• An in vivo assay of growth stimulatory effects was developed, which consisted of microinjecting a RET/ptc2 expression plasmid into the nuclei of 10T1/2 mouse fibroblasts and observing the incorporation of 5-bromodeoxyuridine [2].

Regulatory relationships of Ptch2

• Thus, during mouse development, Ptch2 is expressed in both Shh-producing and -nonproducing cells [5].

Other interactions of Ptch2

• Throughout mouse development, the level of Ptch2 expression is significantly lower than that of Ptch [5].
• Lack of Rb and p53 delays cerebellar development and predisposes to large cell anaplastic medulloblastoma through amplification of N-Myc and Ptch2 [9].
• However, 21 genes were specifically up-regulated in medulloblastoma, including sFrp1, Ptc2, and Math1, members of signaling pathways that regulate cerebellar development [10].

Analytical, diagnostic and therapeutic context of Ptch2

• Shh, Ptc, and Ptch2 were induced about six- to tenfold in normal embryonic hair germs in vivo as well as in developing skin tissue maintained in organ culture [11].

References