A Novel Animal Model for Pseudoxanthoma Elasticum: The KK/HlJ Mouse.

Qiaoli Li
Annerose Berndt
Haitao Guo
John P Sundberg
Jouni Uitto


Pseudoxanthoma elasticum is a multisystem ectopic mineralization disorder caused by mutations in the ABCC6 gene. A mouse model with targeted ablation of the corresponding gene (Abcc6(tm1JfK)) develops ectopic mineralization on the dermal sheath of vibrissae as biomarker of the progressive mineralization disorder. Survey of 31 mouse strains in a longitudinal aging study has identified three mouse strains with similar ectopic mineralization of the vibrissae, particularly the KK/H1J strain. We report here that this mouse strain depicts, in addition to ectopic mineralization of the dermal sheath of vibrissae, mineral deposits in a number of internal organs. Energy dispersive X-ray analysis and topographic mapping found the presence of calcium and phosphate as the principal ions in the mineral deposits, similar to that in Abcc6(tm1JfK) mice, suggesting the presence of calcium hydroxyapatite. The mineralization was associated with a splice junction mutation at the 3' end of exon 14 of the Abcc6 gene, resulting in a 5-bp deletion from the coding region and causing frame-shift of translation. As a consequence, essentially no Abcc6 protein was detected in the liver of the KK/H1J mice, similar to that in Abcc6(tm1JfK) mice. Collectively, our studies found that the KK/H1J mouse strain is characterized by ectopic mineralization due to a mutation in the Abcc6 gene and therefore provides a novel model system to study pseudoxanthoma elasticum.