Mutations in the gene ELOVL4 have been shown to cause stargardt-like macular dystrophy. ELOVL4 is part of a family of fatty acid elongases and is yet to have a specific elongase activity assigned to it. We generated Elovl4 Y270X mutant mice and characterized the homozygous mutant as well as homozygous Elovl4 knockout mice in order to better understand the function or role of Elovl4. We found that mice lacking a functional Elovl4 protein died perinatally. The cause of death appears to be from dehydration due to faulty permeability barrier formation in the skin. Further biochemical analysis revealed a significant reduction in free fatty acids longer than C26 in homozygous mutant and knockout mouse skin. These results implicate the importance of these long chain fatty acids in skin barrier development. Furthermore, we suggest that Elovl4 is likely involved in the elongation of C26 and longer fatty acids.

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The dog-to-sheep renal xenograft model was utilized to isolate the antibodies that participate in xenograft hyperacute rejection. These sheep antibodies, which were isolated from the rejected dog kidney, agglutinated and killed only dog blood and kidney cells whereas the whole sheep serum reacted with both dog and rabbit cells. The purified antibody was also utilized to obtain in pure form the antigens involved in the hyperacute rejection. When this antigen was tested for its ability to bind the serum of various species, this particular antigen was highly specific for sheep serum and would not react with rabbit, horse, calf, or mouse sera.

Hyperacute rejection of xenografts is thought to be triggered by humoral antibodies. It is known that natural antibodies against dog blood cells have been identified in sheep serum. Dog kidney antigen immunoadsorbent columns were placed in the extracorporeal lymph circuit of two sheep. In vivo studies have shown that these immunoadsorbent columns were effective in depleting the thoracic duct lymph of all antibodies with specificity for the dog kidney antigen. However, these columns were not effective in depleting the thoracic duct lymphocytes bearing surface receptors for the dog kidney antigen. When in vitro studies were carried out, the immunoadsorbent columns were effective in the depletion of both lymphocytes and antibody for the dog kidney antigen. Thus, since a humoral antibody response is thought to be responsible for the hyperacute rejection seen in xenografts, it is possible that these columns might be effective in prolonging xenograft survival.