A new Col1a1 conditional knock-in mouse model to study osteogenesis imperfecta.

Autor:	Dimori M; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR., Toulany M; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR., Sultana LS; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR., Onal M; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR., Thostenson JD; Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR., Carroll JL; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR.; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR., O'Brien CA; Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, AR.; Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, AR.; Central Arkansas Veterans Healthcare System, Little Rock, AR., Morello R; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR.; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR.; Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, AR.
Jazyk:	angličtina
Zdroj:	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2024 Nov 20. Date of Electronic Publication: 2024 Nov 20.
DOI:	10.1093/jbmr/zjae189
Abstrakt:	Osteogenesis imperfecta (OI) constitutes a family of bone fragility disorders characterized by both genetic and clinical heterogeneity. Several different mouse models reproduce the classic features of OI, and the most-commonly studied carry either a spontaneous or genetically induced pathogenic variant in the Col1a1 or Col1a2 gene. When OI is caused by primary alterations of type I collagen, it represents a systemic connective tissue disease that, in addition to the skeleton, also affects several extra-skeletal tissues and organs such as skin, teeth, lung, heart, and others, where the altered type I collagen is also expressed. Currently, existing mouse models harbor a disease-causing genetic variant in all tissues and do not allow assessing primary versus secondary consequences of the mutation on a specific organ/system. Here, we describe the generation of the first conditional knock-in allele for Col1a1 that can express a severe OI-causing glycine substitution (p.Gly1146Arg) in the triple helical region of α1(I) but only after Cre-driven recombination in the tissue of choice. We called this new dominant allele Col1a1G1146R-Floxed/+ and introduced it into the murine model. We describe its validation by crossing mice carrying this allele with EIIA-Cre expressing mice and showing that offspring with the recombined allele reproduce the classic features of a severe form of OI. The new mouse model will be useful to study the tissue-specific impact of this severe mutation on organs such as the lung, the heart and others. (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)
Databáze:	MEDLINE
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