Steven Bruce Carroll

US Patent:

6602851, Aug 5, 2003

Filed:

Oct 6, 2000

Appl. No.:

09/684708

Inventors:

Steven L. Carroll - Homewood AL

Assignee:

UAB Research Foundation - Birmingham AL

International Classification:

A61K 3818

US Classification:

514 12, 514903, 530350

Abstract:

Distinct cDNAs encoding six cysteine-rich domain-NRGs and four glial growth factor isoforms were identified and sequenced. Additional heterogeneity is found in the EGF-like (- and -isoforms) and carboxy terminal (a and b variant) regions of CRD-NRGs. Furthermore, the predicted GGF proteins contain glycosylation domains previously found only in mesenchymal NRGs. GGF mRNAs accumulate in axotomized nerve, a subpopulation of DRG neurons and most spinal cord motoneurons. CRD-NRGs, however, are undetectable in injured nerve except by RT-PCR. In contrast, the majority of DRG and spinal cord motor neurons express CRD-NRGs, with a 1 isoform being most abundant and at least some of these proteins are secreted in a form capable of activating erbB receptors. Thus, GGF and CRD-NRG subfamilies are more structurally diverse than previously appreciated. NRG actions during Wallerian degeneration may be modulated by the action of distinct splice variants.