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The baboon: a model for the study of primate growth hormone receptor gene expression during development
G Zogopoulos1, P Nathanielsz, G N Hendy
1Department of Pediatrics, McGill University, Montreal, Québec, Canada.
Insights
The baboon is a suitable model for studying human growth hormone receptor (GHR) gene transcription. Baboon GHR gene expression patterns during development mirror human development, unlike subprimates.
Area of Science:
- Primate developmental biology
- Molecular endocrinology
- Comparative genomics
Background:
- Growth hormone receptor (GHR) expression differs significantly between humans and subprimates during development.
- Subprimates are inadequate models for studying human GHR gene regulation, especially in early development.
Purpose of the Study:
- To evaluate the baboon as a suitable animal model for investigating human GHR gene transcription regulation.
- To compare baboon GHR gene expression patterns with those in humans during development.
Main Methods:
- Cloning of baboon GHR cDNAs using reverse transcription (RT)-PCR with human GHR-specific primers.
- Analysis of baboon GHR mRNA 5' untranslated region (UTR) variants (V1, V3, V4) and their sequence identity to human counterparts.
- Characterization of the expression patterns of GHR mRNA isoforms in baboon liver, kidney, and lung during different developmental stages.
Main Results:
- Baboon GHR precursor protein and mature GHR show high amino acid identity to human and rhesus monkey GHRs.
- Baboon GHR mRNA 5' UTR variants V1, V3, and V4 share high sequence identity with human variants.
- Baboon V1 and V4 expression is developmentally regulated and tissue-specific, similar to humans, while V3 is more widely expressed across tissues and developmental stages.
Conclusions:
- The regulatory regions of baboon and human GHR genes are likely well-conserved.
- The baboon serves as an appropriate animal model for defining mechanisms regulating GHR gene transcription during primate development.
Abstract:
In subprimates, significant onset of growth hormone receptor (GHR) expression 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 GHR gene transcription, especially during early stages in development. Here we have explored the potential of the baboon as a more appropriate model. Baboon 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 rhesus monkey GHRs, and the mature baboon GHR is also 620 amino acids long, with 95% and 98.5% amino acid identity to the human and rhesus monkey receptors respectively. Previous studies in the human have identified eight 5' untranslated region (5' UTR) variants of the GHR mRNA (V1 to V8, numbered according to their relative abundance). We cloned the baboon V1, V3 and V4 homologues by RT-PCR: these variants have a high degree (>92%) of sequence identity with their human counterparts and also diverge at an identical point, 12 nucleotides upstream of the start of translation. The expression pattern of these three GHR mRNA isoforms in baboon liver during development was characterized. 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 days gestation) and postnatal (n=7, 6-19.6 days and adult (18.6 kg)) hepatic specimens 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 and V4. Together, these data demonstrate that, as in the human, baboon V1 and V4 expression is developmentally regulated and tissue specific, while the V3 isoform is more widely expressed. Therefore, it is likely that the regulatory regions of the baboon and human GHR genes are well conserved. Our findings suggest that the baboon is an appropriate animal model in which to define the mechanisms regulating GHR gene transcription during primate development.
