Developmental abnormalities in transgenic mice expressing a sialic acid-specific 9-O-acetylesterase.
9-O-acetylation of sialic acids is tissue specific and developmentally regulated. We have selectively destroyed these O-acetyl groups during murine embryogenesis by expressing the 9-O-acetyl-sialic acid-specific esterase of influenza C. DNA constructs driven by the metallothionein promoter arrested development at the 2-cell stage and gave a markedly decreased yield of live mice. A similar construct driven by the phenylethanolamine-N-methyltransferase promoter did not cause this block, but gave transgenic mice with selective expression of esterase in the retina and the adrenal gland. These organs showed variable abnormalities in organization, while all other tissues examined appeared normal. The ganglioside 9-O-acetyl-GD3 was selectively destroyed in target tissues. Thus, 9-O-acetylated sialic acids may play an role in murine development at the 2-cell stage and in certain differentiated tissues.
Varki
A
A
Department of Medicine, University of California, San Diego 92093.
Hooshmand
F
F
Diaz
S
S
Varki
N M
NM
Hedrick
S M
SM
D000107:Acetylation; D000115:Acetylesterase; D000311:Adrenal Glands / Q000002:abnormalities / Q000201:enzymology; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005314:Embryonic and Fetal Development / Q000502:physiology*; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008845:Microinjections; D009928:Organ Specificity; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012160:Retina / Q000002:abnormalities / Q000201:enzymology; D012794:Sialic Acids / Q000378:metabolism / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms
D012794:Sialic Acids; D008668:Metallothionein; D010625:Phenylethanolamine N-Methyltransferase; D002265:Carboxylic Ester Hydrolases; D000115:Acetylesterase; C046298:sialate O-acetylesterase