Data for: Actions of Parathyroid hormone ligand analogs in humanized PTH1R knock-in mice

Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogs for their pharmacologic activities and potential therapeutic utility towards 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 versus 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 pre-clinical evaluations.  To overcome this potential uncertainty, we used a homologous recombination-based knock-in (KI) approach to generate a mouse (in host strain C57Bl/6N) in which cDNA encoding the human PTH1R replaces a segment (Exon 4) of the murine PTH1R gene such that the human and not the mouse PTH1R protein is expressed. Expression is..., PTH Peptides 
The peptides PTH(1-34) (SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF), PTHrP(1-36) (AVSEHQLLHDKGKSIQDLRRRFFLHHLIAEIHTAEI); LA-PTH(7-36) (LnLHQLdWKWIQDARRRAWLHKLIAEIHTAEI; nL = norleucine) or [Leu11,dTrp12,Trp23,Tyr36]-PTHrP(7-36) (LLHDLdWKSIQDLRRRFWLHHLIAEIHTAEY; dW = d-tryptophan), were synthesized as C-terminal amides by the Massachusetts General Hospital Biopolymer Core facility. Peptides were purified by HPLC and confirmed for identity by mass spectroscopy. Abaloparatide (AVSEHQLLHDKGKSIQDLRRRELLEKLLbKLHTA; b = aminoisobutyric acid) was produced at Lonza (reference # 2AK1F). Peptides were dissolved in 10 mM acetic acid to a stock peptide concentration of 1.0 mM, and aliquots of the stock solutions were stored at -80˚C.
Generation of hPTH1R-KI Mice
Mouse lines were generated at Cyagen Biosciences Inc. (Santa Clara, Ca) using a homologous recombination-based knock-in strategy (see Figure 1). To engineer the targeting vector, homology arms were generated by PCR using BAC clone RP24..., ,