Spontaneous calcification in hearts of DBA mice

Abstract

Onset, frequency and characteristics of the spontaneous calcification which occurs in hearts of mice of the DBA strain have been studied. Calcified myocardial lesions developed as early as 25 days of age. A limited inflammatory response was associated with the fine mineral granules of early lesions. With age, sites of calcium deposition became larger and agranular. There was no evidence of inflammation at such loci and adjacent connective tissue did not increase significantly. In the oldest animals (older than 90 days), fibrous encapsulation of calcified sites was typical. Calcareous epicarditis appeared by 30 days; was minimal (8% ) through 90 days, and then rose sharply in incidence (50% ) in older animals. Epicardial calcification was restricted to the right ventricle. In general the calcified lesions increased with age and were not related to sex. Incidence of all lesions was 17% by 30 days of age, 80% within 90 days, and 94% in mice older than 90 days.Many cardiomyopathies are characterized by deposition of calcium (Bajusz, '65; Reichenbach and Benditt, '68). Alterations in mineral metabolism that participate in this focal calcification remain obscure (Selye, '62). The DBA strain of mice, which has a high incidence of spontaneous calcareous lesions (Morris, Dunn and Wagner, '53; Hare and Stewart, '56; DiPaolo, Strong and Moore, '64; Ball and Williams, '65), provides excellent material for the study of calcinosis of soft tissue. Ventricular myocardial calcification developed in 32% of the mice while the incidence of epicardial calcification was 12% (Ball and Williams, '65). These calcified lesions do not reduce longevity, or alter susceptibility or resistance to diet-induced cardiac damage (Ball and Williams, '65).First, this study attempts to show the presence and extent of spontaneous cardiac calcification. The purpose of the second part of the study was to demonstrate the natural history of such calcification in male and female DBA mice. Mice representing an age range of 1-90 days were killed at intervals to establish chronological progression of the calcification. Such lesions in these younger mice were compared with those in animals older than 90 days. MATERIALS AND METHODSMembers of the DBA/2J (Jackson Memorial Laboratory) strain of mice were used. Their diet was a stock commercial ration consisting of approximately 25% protein, 6% fat, 47% carbohydrate, and containing adequate amounts of vitamins and minerals. This well balanced ration is adequate for growth, reproduction and lactation. Housing and care of the mice were optimum.Group I was composed of 36 female retired breeders (over 90 days of age) that were used in a study of the capacities of fixatives and stains to characterize the lesions. In group I1 there were 111 mice killed at ages of 1-90 days to ascertain onset of the lesions and their subsequent history ( fig. 1). Histological methodsMice were killed by cervical compression. Tissues were fixed, dehydrated and embedded in paraffin in the usual manner. Frontal sections (8 p) were mad...

Toxicity of LY303366, an Echinocandin Antifungal, in Mice Pretreated with Glucocorticoids

“…In DBA/2 mice, a calcific embolic material was noted in the tissue sections, particularly in the kidneys. These findings may or may not be important, as there are reports in the literature of spontaneous calcification in the heart in this strain of mice (4,6). However, in our study only those survivors from groups given a steroid and LY in which lethal toxicity occurred showed these pathological abnormalities.…”

A locus on chromosome 7 determines myocardial cell necrosis and calcification (dystrophic cardiac calcinosis) in mice.

“…Age-related spontaneous dystrophic cardiac calcinosis (DCC) occurs in several inbred strains of mice, including BALB/c, DBA/2, and C3H; DCC may even lead to congestive heart failure in older animals (9)(10)(11)(12). Apart from age and genetic background, other factors including infectious agents (13)(14)(15), sex (9,12), hormonal status (9,(16)(17)(18), and diet (1,9,(19)(20)(21) can markedly influence the time of onset and the severity of DCC.…”

Protein synthesis inhibition and cardiac lesions associated with deoxynivalenol ingestion in mice

“…Since the same cardiac lesions, frequently associated with myocardial calcifications, have been described as occurring spontaneously (Ball and Williams 1965;Nabors and Ball 1969) in certain strains of mice (in particular DBA), some authors (Dipaolo et al 1964;Nabors and Ball 1969) claim that there is a genetic susceptibility. The incidence of these lesions increases with age (Nabors and Ball 1969). In our study, epicardial calcifications did not seem to have the same characteristics as spontaneous ones: indeed, these strictly epicardial lesions, absent in control animals, were found in young (2 months) Balb/c mice after DON ingestion.…”