ArticleEndocrinology2022
Actions of Parathyroid Hormone Ligand Analogues in Humanized PTH1R Knockin Mice.
Article in Endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Spatial control of parathyroid hormone receptor-1 signaling dictates ligand-specific biological outcomes.Signal transduction and targeted therapy · 2026Article
- A novel brachydactyly type E syndrome caused by variants in helix 8 of the PTH1R.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Jansen's Disease: Bone Abnormalities Beyond Chondrodysplasia.The Journal of clinical endocrinology and metabolism · 2025Article
- The evolution of hominin bipedalism in two steps.Nature · 2025Article
- Humanized mice to model rare human diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A mouse model of Jansen's metaphyseal chondrodysplasia for investigating disease mechanisms and candidate therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Prolonging parathyroid hormone analog action in vitro and in vivo through peptide lipidation.Nature communications · 2025Article
- The Evolving Role of PTH Signaling in Osteocytes.Endocrinology · 2025Review
- Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogues for their pharmacologic activities and potential therapeutic utility toward diseases of bone and mineral ion metabolism. Divergence, however, in the amino acid sequences of rodent and human PTH receptors (rat and mouse PTH1Rs are 91% identical to the human PTH1R) can lead to differences in receptor-binding and signaling potencies for such ligands when assessed on rodent vs human PTH1Rs, as shown by cell-based assays in vitro. This introduces an element of uncertainty in the accuracy of rodent models for performing such preclinical evaluations. To overcome this potential uncertainty, we used a homologous recombination-based knockin (KI) approach to generate a mouse (in-host strain C57Bl/6N) in which complementary DNA encoding the human PTH1R replaces a segment (exon 4) of the murine PTH1R gene so that the human and not the mouse PTH1R protein is expressed. Expression is directed by the endogenous mouse promoter and hence occurs in all biologically relevant cells and tissues and at appropriate levels. The resulting homozygous hPTH1R-KI (humanized) mice were healthy over at least 10 generations and showed functional responses to injected PTH analog peptides that are consistent with a fully functional human PTH1R in target bone and kidney cells. The initial evaluation of these mice and their potential utility for predicting behavior of PTH analogues in humans is reported here.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.