Composition and synthesis of polyunsaturated fatty acyl groups in the embryonic brain of the trisomy-16 mouse

Abstract

The trisomy-16 (T-16) mouse is considered to be a promising model for human trisomy-21 (T-21) (Down's syndrome, DS). Therefore, the fatty acyl (PUFA) compositions of phosphoglycerides in embryonic brains (days E-17 and E-18) of T-16 mice have been compared with those of balanced heterozygotic embryos from the same litters, in order to determine whether similar abnormalities are present as have been found in foetal DS brain (Brooksbank et al., 1985, J. Neurochem.44, 869–874). The analyses revealed that the ratio of (n-3) to (n-6) PUFA was significantly increased in ethanolamine (EPG) and in choline phosphoglycerides, as it is in EPG in the foetal T-21 brain. However, the abnormality was not so marked in the murine as in the human trisomy, and the (n-3)(n-6) ratio in EPG was primarily elevated on account of decreased proportions of 20:4(n-6) and 22:4(n-6), there being no significant increase in (n-3) PUFA. The PUFA composition of the phosphoglycerides of the corresponding trisomic and balanced placentae was also determined, but no relevant differences could be discerned between the genetically different tissues.As 6-desaturase, the rate-limiting enzyme system in PUFA synthesis, reacts more readily with (n-3) than with (n-6) substrates, the shift in (n-3)(n-6) ratio of PUFA might be related to an alteration in 6-desaturase activity in trisomy. Comparison of the specific activity of 6-desaturase in fresh brain homogenates of T-16 embryos with those from balanced litter-mates revealed, however, no differences.