Using the Drosophila gene Dmel\SPARC, fly models have been used to assess the contribution of SPARC in the development of cardiomyopathy and age-related cardiac dysfunction. There are two orthologous genes of Dmel\SPARC in human, designated SPARC and SPARCL1. SPARC encodes a matrix-associated protein that appears to regulate cell growth through interactions with the extracellular matrix and cytokines. The human SPARC gene is implicated in a form of osteogenesis (MIM:6165070).
A UAS construct of human Hsap\SPARC has been introduced into flies, but has not been characterized.
Using a Drosophila model of cardiomyopathy induced by loss of pericardial nephrocytes (see FBhh0000554), a significant increase in the circulating level of SPARC protein was observed. Animals with nephrocyte loss and also heterozygous for a loss-of-function mutation of Dmel\SPARC exhibit normal heart function. In subsequent experiments it was observed that in young adult animals over-expression of Dmel\SPARC in pericardial nephrocytes results in both cardiomyopathy and increased cardiac collagen deposition.
Similar to humans, aging Drosophila exhibit reduced cardiac function and heart tissue fibrosis, an accumulation of extracellular matrix proteins such as collagen. It is postulated that increased collagen accumulation is a key causative factor in the development of age-related heart dysfunction. Assessing cardiac aging in older flies, it was observed that animals heterozygous for a loss-of-function mutation of Dmel\SPARC live longer than controls and show little to no age-related cardiac dysfunction. However, age-related accumulation of cardiac collagen is still observed in these animals. Thus the protective effect of reduced levels of SPARC appears to be mediated by mechanisms other than reduced accumulation of collagen.
[updated Feb. 2021 by FlyBase; FBrf0222196]
SPARC encodes a cysteine-rich acidic matrix-associated protein; it appears to regulate cell growth through interactions with the extracellular matrix and cytokines. Binds calcium and copper, several types of collagen, albumin, thrombospondin, PDGF and cell membranes. [Gene Cards, SPARC; 2021.02.03]
Many to one: 2 human genes to 1 Drosophila gene.
High-scoring ortholog of human SPARC; moderate-scoring ortholog of human SPARCL1 (1 Drosophila to 2 human). Dmel\SPARC shares 28% identity and 41% similarity with SPARC; these 2 proteins are comparable in size. SPARCL1 encodes a much larger protein.
