Overexpression of TGF-beta 1 in the central nervous system of transgenic mice results in hydrocephalus.
Transforming growth factor beta (TGF-beta) has been proposed to play a number of roles in central nervous system (CNS) development and response to injury. To test these proposals, transgenic mice were generated which overproduce TGF-beta 1 in the CNS. Surprisingly, these mice developed severe hydrocephalus and died between birth and 3 weeks of age. Ovary transplantation from an affected female founder has permitted perpetuation of one of the lines as a hydrocephalus model whose genetic defect is known. These results also demonstrate that the developing CNS is highly sensitive to TGF-beta, and suggest a role for aberrant expression of TGF-beta in the pathogenesis of developmental disease of the CNS.
Galbreath
E
E
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA.
Kim
S J
SJ
Park
K
K
Brenner
M
M
Messing
A
A
D000818:Animals; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006849:Hydrocephalus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta