Perspective: The current state of Cre driver mouse lines in skeletal research: Challenges and opportunities.
Cre
Floxed allele
LoxP
Recombination
Skeletal models
Journal
Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
28
12
2022
revised:
15
02
2023
accepted:
19
02
2023
pmc-release:
01
05
2024
pubmed:
4
3
2023
medline:
21
3
2023
entrez:
3
3
2023
Statut:
ppublish
Résumé
The Cre/Lox system has revolutionized the ability of biomedical researchers to ask very specific questions about the function of individual genes in specific cell types at specific times during development and/or disease progression in a variety of animal models. This is true in the skeletal biology field, and numerous Cre driver lines have been created to foster conditional gene manipulation in specific subpopulations of bone cells. However, as our ability to scrutinize these models increases, an increasing number of issues have been identified with most driver lines. All existing skeletal Cre mouse models exhibit problems in one or more of the following three areas: (1) cell type specificity-avoiding Cre expression in unintended cell types; (2) Cre inducibility-improving the dynamic range for Cre in inducible models (negligible Cre activity before induction and high Cre activity after induction); and (3) Cre toxicity-reducing the unwanted biological effects of Cre (beyond loxP recombination) on cellular processes and tissue health. These issues are hampering progress in understanding the biology of skeletal disease and aging, and consequently, identification of reliable therapeutic opportunities. Skeletal Cre models have not advanced technologically in decades despite the availability of improved tools, including multi-promoter-driven expression of permissive or fragmented recombinases, new dimerization systems, and alternative forms of recombinases and DNA sequence targets. We review the current state of skeletal Cre driver lines, and highlight some of the successes, failures, and opportunities to improve fidelity in the skeleton, based on successes pioneered in other areas of biomedical science.
Identifiants
pubmed: 36868507
pii: S8756-3282(23)00052-2
doi: 10.1016/j.bone.2023.116719
pmc: PMC10087282
mid: NIHMS1880532
pii:
doi:
Substances chimiques
Cre recombinase
EC 2.7.7.-
Integrases
EC 2.7.7.-
Recombinases
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
116719Subventions
Organisme : BLRD VA
ID : I01 BX001478
Pays : United States
Organisme : BLRD VA
ID : IK6 BX003783
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR053237
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR065971
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest All authors have declared that no conflicts of interest exist. Financial support was provided by the NIH (AR053237 to AGR; AG069489 to RBC) and the US Department of Veterans Affairs (BX001478, IK6 BX003783, and I01 BX005861 to AGR).
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