Although known for almost 80 years, the physiological role of plasmalogens (PLs), the major @entity1 ether lipids (ELs), is still enigmatic. @entity1 that lack ELs suffer from @entity20722 ( @entity20722 ), a @entity16440 usually resulting in @entity204 in early childhood. In order to learn more about the functions of ELs, we generated a @entity19 model for @entity20722 by a targeted disruption of the @entity12036 acyltransferase gene. The mutant @entity19 revealed @entity156 , such as @entity4810 , @entity735 , @entity231 and @entity1781 , some of which were also observed in @entity20722 . Mass spectroscopic analysis demonstrated the presence of highly @entity1474 including @entity4600 ( @entity4601 ) in brain PLs and the occurrence of PLs in lipid raft microdomains (LRMs) isolated from brain myelin. In mutants, PLs were completely absent and the concentration of brain @entity4601 was reduced. The marker proteins @entity70492 /contactin were found in brain LRMs in reduced concentrations. In addition, the gap junctional protein @entity16899 , known to be recruited to LRMs and essential for lens development and spermatogenesis, was down-regulated in embryonic fibroblasts of the EL-deficient @entity19 . Free @entity165 , an important constituent of LRMs, was found in these fibroblasts to be accumulated in a perinuclear compartment. These data suggest that the EL-deficient @entity19 allow the identification of new phenotypes not related so far to @entity942 ( @entity4810 , defects in myelination and @entity1781 ) and indicate that PLs are required for the correct assembly and function of LRMs.

Inactivation of ether lipid biosynthesis causes XXXX , @entity735 and @entity1781 in @entity19 .

@entity1 :: ('9606', 'Species') :: ['mammalian', 'Humans'] @entity16899 :: ('14609(Tax:10090)', 'Gene') :: ['connexin 43'] @entity20722 :: ('MESH:D018902', 'Disease') :: ['RCDP', 'rhizomelic chondrodysplasia punctata'] @entity16440 :: ('MESH:D018901', 'Disease') :: ['peroxisomal disorder'] @entity4810 :: ('MESH:D007248', 'Disease') :: ['male sterility', 'male infertility'] @entity231 :: ('MESH:D002386', 'Disease') :: ['cataract'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity4600 :: ('CHEBI:28125', 'Chemical') :: ['docosahexaenoic acid'] @entity12036 :: ('MESH:D004099', 'Chemical') :: ['dihydroxyacetonephosphate'] @entity942 :: ('MESH:D003677', 'Disease') :: ['EL-deficiency'] @entity156 :: ('MESH:D000015', 'Disease') :: ['multiple abnormalities'] @entity1474 :: ('MESH:D005231', 'Chemical') :: ['unsaturated fatty acids'] @entity70492 :: ('14251(Tax:10090)', 'Gene') :: ['flotillin-1 and F3'] @entity735 :: ('MESH:D005124', 'Disease') :: ['defects in eye development'] @entity4601 :: ('CHEBI:16016', 'Chemical') :: ['DHA'] @entity1781 :: ('MESH:D009901', 'Disease') :: ['optic nerve hypoplasia'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']
@entity4810 :: (MESH:D007248,Disease) :: ['male infertility']
