The baboon: a model for the study of primate growth hormone receptor gene expression during development

In subprimates, significant onset of growth hormone receptor (GHR) expressi on occurs only after birth whereas, in the human, GHR mRNA and protein are widely manifest from the first trimester of fetal life. Thus, it is likely that subprimates are not the best models for studying regulation of human G HR gene transcription, especially during early stages in development. Here we have explored the potential of the baboon as a more appropriate model. B aboon GHR cDNAs were cloned from postnatal liver by reverse transcription ( RT)-PCR, using human GHR-specific primers. The encoded baboon GHR precursor protein has an identical signal peptide sequence to that of human and rhes us monkey GHRs, and the mature baboon GHR is also 620 amino acids long, wit h 95% and 98.5% amino acid identity to the human and rhesus monkey receptor s respectively. Previous studies in the human have identified eight 5' untr anslated region (5' UTR) variants of the GHR mRNA (V1 to V8, numbered accor ding to their relative abundance). We cloned the baboon V1, V3 and V4 homol ogues by RT-PCR: these variants have a high degree (>92%) of sequence ident ity with their human counterparts and also diverge at an identical point, 1 2 nucleotides upstream of the start of translation. The expression pattern of these three GHR mRNA isoforms in baboon liver during development was cha racterized. Strong expression of baboon V1 and V4 was evident by 49 days of postnatal life (n=5, 49 days and adult (18.6-19.6 kg)); very low levels of V1, but not V4, were observed in younger animals (n=2, 6 and 30 days). In contrast, V3 5' UTR variant mRNA was present in all fetal (n=4, 141-155 day s gestation) and postnatal (n=7, 6-19.6 days and adult (18.6 kg)) hepatic s pecimens examined. Analysis of postnatal kidney and lung (n=2, 19 and 19.6 kg) revealed that V3 transcripts are present in these tissues, but not V1 a nd V4. Together, these data demonstrate that, as in the human, baboon V1 an d V4 expression is developmentally regulated and tissue specific, while the V3 isoform is more widely expressed. Therefore, it is likely that the regu latory regions of the baboon and human GHR genes are well conserved. Our fi ndings suggest that the baboon is an appropriate animal model in which to d efine the mechanisms regulating GHR gene transcription during primate devel opment.