title: Two Techniques to Create Hypoparathyroid Mice: Parathyroidectomy Using GFP Glands and Diphtheria-Toxin-Mediated Parathyroid Ablation.
abstract: Hypoparathyroidism (HP) is a disorder characterized by low levels of PTH which lead to hypocalcemia, hyperphosphatemia, and low bone turnover. The most common cause of the disease is accidental removal of the parathyroid glands during thyroid surgery. Novel therapies for HP are needed, but testing them requires reliable animal models of acquired HP. Here, we demonstrate the generation of two mouse models of acquired HP. In the GFP-PTX model, mice with green fluorescent protein (GFP) expressed specifically in the parathyroids (PTHcre-mTmG) were created by crossing PTHcre+mice with Rosa-mTmGfl/flmice. Green fluorescing parathyroid glands are easily identified under a fluorescence dissecting microscope and parathyroidectomy is performed in less than 20 min. After fluorescence-guided surgery, mice are profoundly hypocalcemic. Contrary to the traditional thyro-parathyroidectomy, this precise surgical approach leaves thyroid glands and thyroid function intact. The second model, which does not require surgery, is based on a diphtheria-toxin approach. PTHcre-iDTR mice, which express the diphtheria toxin (DT) receptor specifically in the parathyroids, were generated by crossing the inducible DTR mouse with the PTHcre mouse. Parathyroid cells are thus rendered sensitive to diphtheria toxin (DT) and can be selectively destroyed by systemically injecting mice with DT. The resulting hypocalcemic phenotype is stable.
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School; West China School of Stomatology, Sichuan University.
authors.forename: Ruiye
authors.initials: R
authors.lastname: Bi
authors.affiliation: West China School of Stomatology, Sichuan University; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fan
authors.affiliation: West China School of Stomatology, Sichuan University; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.
authors.forename: En
authors.initials: E
authors.lastname: Luo
authors.affiliation: West China School of Stomatology, Sichuan University; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Harvard Medical School; mannstadt@mgh.harvard.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Mannstadt
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood; D004167:Diphtheria Toxin / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D007011:Hypoparathyroidism / Q000097:blood / Q000209:etiology*; D049408:Luminescent Agents / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010280:Parathyroid Glands / Q000187:drug effects* / Q000601:surgery*; D010281:Parathyroid Hormone / Q000097:blood; D016105:Parathyroidectomy / Q000379:methods*; D011042:Poisons
chemical_list: D004167:Diphtheria Toxin; D049408:Luminescent Agents; D010281:Parathyroid Hormone; D011042:Poisons; D002118:Calcium