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Mouse models for pseudoxanthoma elasticum: Genetic and dietary modulation of the ectopic mineralization phenotypes

Li, Q and Guo, H and Chou, DW and Berndt, A and Sundberg, JP and Uitto, J (2014) Mouse models for pseudoxanthoma elasticum: Genetic and dietary modulation of the ectopic mineralization phenotypes. PLoS ONE, 9 (2).

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Abstract

Pseudoxanthoma elasticum (PXE), a heritable ectopic mineralization disorder, is caused by mutations in the ABCC6 gene. Null mice ( Abcc6 -/-) recapitulate the genetic, histopathologic and ultrastructural features of PXE, and they demonstrate early and progressive mineralization of vibrissae dermal sheath, which serves as a biomarker of the overall mineralization process. Recently, as part of a mouse aging study at The Jackson Laboratory, 31 inbred mouse strains were necropsied, and two of them, KK/HlJ and 129S1/SvImJ, were noted to have vibrissae dermal mineralization similar to Abcc6-/- mice. These two strains were shown to harbor a single nucleotide polymorphism (rs32756904) in the Abcc6 gene, which resulted in out-of-frame splicing and marked reduction in ABCC6 protein expression in the liver of these mice. The same polymorphism is present in two additional mouse strains, DBA/2J and C3H/HeJ, with similar reduction in Abcc6 protein levels, yet these mice did not demonstrate tissue mineralization when kept on standard rodent diet. However, all four mouse strains, when placed on experimental diet enriched in phosphate and low in magnesium, developed extensive ectopic mineralization. These results indicate that the genetic background of mice and the mineral composition of their diet can profoundly modulate the ectopic mineralization process predicated on mutations in the Abcc6 gene. These mice provide novel model systems to study the pathomechanisms and the reasons for strain background on phenotypic variability of PXE. © 2014 Li et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Li, Q
Guo, H
Chou, DW
Berndt, A
Sundberg, JP
Uitto, J
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSato, MakotoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 19 February 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0089268
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Date Deposited: 18 Jun 2014 19:53
Last Modified: 02 Feb 2019 13:55
URI: http://d-scholarship.pitt.edu/id/eprint/21910

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