Dystrophic cardiac calcification (DCC) is an autosomal recessive trait characterized by calcium phosphate deposits in myocardial tissue. The Abcc6 gene locus was recently found to mediate DCC; however, at the molecular level the causative variants remain to be determined. Examining the sequences of Abcc6 cDNA in DCC-resistant C57BL/6 and DCC-susceptible C3H/He mice, we identified a missense mutation (Cys to Thr at codon 619, rs32756904) at the 3-border of exon 14 that creates an additional donor splice site (GT). Accordingly, an alternative transcript variant was detected, lacking the last 5 bp of exon 14 (-AGG(C/T)GCTgtga-) in DCC-susceptible C3H/He mice that carry the Thr allele. The 5-bp deletion was found to result in premature termination at codon 684, in turn leading to protein deficiency in DCC-susceptible mouse tissue as well as in cells transfected with Abcc6 cDNA lacking the last 5 bp of exon 14. All mouse strains that were found to carry the Thr allele, including C3H/He, DBA/2J, and 129S1/SvJ, were also found to be positive for DCC. In summary, we identified a splice variant leading to a 5-bp deletion in the Abcc6 transcript that gives rise to protein deficiency both in vivo and in vitro. The fact that all mouse strains that carry the deletion also develop dystrophic calcifications further suggests that the underlying splice variant affects the biological function of MRP6 protein and is a cause of DCC in mice.

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T cells play an important role in protective immune responses and in the pathogenesis of many diseases. Understanding the mechanisms regulating their distribution in vivo may therefore be of therapeutic value. Reviewing studies that have followed the migration of labelled naive, effector and memory T cells in healthy animals reveals that all T-cell subsets enter all organs investigated. Within the tissue, two principally different migration patterns can be identified. First, naive and memory T cells accumulate in lymphoid organs for about 48 h after injection, as the time needed for migration through lymphoid organs is longer than through non-lymphoid organs. During this time, surface molecule expression is temporarily modified. These changes are reversed before leaving the lymphoid organs and entering the blood to start a new cycle of migration. Second, effector T cells are evenly distributed throughout the body, and most die in the tissues within 24 h. However, depending on the presence of cytokines, some are able to survive and to proliferate, and thereby accumulate in defined microenvironments of the body. Analysing the principles regulating T-cell migration and survival within the tissue may lead to the development of new options for the treatment of disease.

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