IDENTIFICATION OF NOVEL VARIANTS OF TRKC MESSENGER-RNA TRANSCRIPTS INBRAIN OF AFRICAN-GREEN MONKEYS

The distinct biological effects of neurotrophins are mediated in part through their binding to the high-affinity neurotrophin receptors repr esented by the Trk family of receptor tyrosine kinases. Using the tech nique of reverse transcriptase-polymerase chain reaction (RT-PCR), we cloned several partial cDNAs encoding trkA, trkB, and trkC from fetal brains of African green monkeys. Southern analysis of PCR products sho wed that the ventral tegmental area of adult monkey and ventral midbra ins of fetal monkeys of E59, E81, E91, and E150 days of gestation expr essed all three trk gene transcripts, whereas only trkB and trkC mRNAs were detectable in the adult substanta nigra The nucleotide sequences of the cloned monkey trh cDNAs are highly homologous to their human c ounterparts, and we detected a splice variant of trkC that has recentl y been described in humans, but not in rodents. Moreover, sequencing o f trkC cDNAs derived from four fetal monkey midbrains revealed two nov el variants with single nucleotide substitution. A missense mutation ( AAT to AGT) was identified in the codon corresponding to codon 361 of the deduced human TrkC sequence, converting an encoded Asn to Ser. The second variant involves a silent transition at the third nucleotide o f the codon Gly 362 (GGC to GGA). Furthermore, three of the four poten tial alleles involving these two trkC variants were detected in these monkeys, indicating that a segregation of multiple trkC alleles occurs in a geographically contained population of feral monkeys. (C) 1997 A cademic Press