A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration (WldS) mouse.
Exons of three genes were identified within the 85-kilobase tandem triplication unit of the slow Wallerian degeneration mutant mouse, C57BL/Wld(S). Ubiquitin fusion degradation protein 2 (Ufd2) and a previously undescribed gene, D4Cole1e, span the proximal and distal boundaries of the repeat unit, respectively. They have the same chromosomal orientation and form a chimeric gene when brought together at the boundaries between adjacent repeat units in Wld(S). The chimeric mRNA is abundantly expressed in the nervous system and encodes an in-frame fusion protein consisting of the N-terminal 70 amino acids of Ufd2, the C-terminal 302 amino acids of D4Cole1e, and an aspartic acid formed at the junction. Antisera raised against synthetic peptides detect the expected 43-kDa protein specifically in Wld(S) brain. This expression pattern, together with the previously established role of ubiquitination in axon degeneration, makes the chimeric gene a promising candidate for Wld. The third gene altered by the triplication, Rbp7, is a novel member of the cellular retinoid-binding protein family and is highly expressed in white adipose tissue and mammary gland. The whole gene lies within the repeat unit leading to overexpression of the normal transcript in Wld(S) mice. However, it is undetectable on Northern blots of Wld(S) brain and seems unlikely to be the Wld gene. These data reveal both a candidate gene for Wld and the potential of the Wld(S) mutant for studies of ubiquitin and retinoid metabolism.
Conforti
L
L
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom.
Tarlton
A
A
Mack
T G
TG
Mi
W
W
Buckmaster
E A
EA
Wagner
D
D
Perry
V H
VH
Coleman
M P
MP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002490:Central Nervous System / Q000378:metabolism; D018076:DNA, Complementary; D005091:Exons; D005656:Fungal Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D017933:Peripheral Nervous System / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D012177:Retinol-Binding Proteins / Q000235:genetics*; D054840:Retinol-Binding Proteins, Cellular; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D044763:Ubiquitin-Conjugating Enzymes; D014855:Wallerian Degeneration
D018076:DNA, Complementary; D005656:Fungal Proteins; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; C521400:Rbp7 protein, mouse; C114683:UFD2 protein, S cerevisiae; C510972:Nmnat1 protein, mouse