Purkinje cell degeneration associated with erythroid ankyrin deficiency in nb/nb mice.
Mice homozygous for the nb mutation (Chromosome 8) have a severe hemolytic anemia and develop a psychomotor disorder at 6 mo of age. The nb/nb mice are deficient in erythroid ankyrin (Ank-1) but, until the present study, the role of Ank-1 and of Ank-2 (brain ankyrin) in disease genesis was unknown. In normal erythroid tissues, we show that two major transcripts are expressed from Ank-1, and one of these is also present at high levels in the cerebellum. By in situ hybridization and immunocytochemistry, Ank-1 localizes to the cerebellar Purkinje cells and, to a lesser extent, the granule cells. In nb/nb mice, Ank-1 transcripts are markedly reduced in both erythroid and neural tissue, and nb/nb Purkinje cells and granule cells are nearly devoid of Ank-1. The neurological syndrome appears concurrently with a dramatic loss of Purkinje cells. Ank-2 maps to Chromosome 3 and its expression is unaffected by the nb mutation. We conclude that Ank-1 is specifically required for Purkinje cell stability and, in its absence, Purkinje cell loss and neurological symptoms appear.
Peters
L L
LL
Jackson Laboratory, Bar Harbor, Maine 04609.
Birkenmeier
C S
CS
Bronson
R T
RT
White
R A
RA
Lux
S E
SE
Otto
E
E
Bennett
V
V
Higgins
A
A
Barker
J E
JE
D000743:Anemia, Hemolytic / Q000097:blood / Q000235:genetics / Q000473:pathology; D000818:Animals; D017487:Ankyrins; D001798:Blood Proteins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D001921:Brain / Q000502:physiology / Q000503:physiopathology*; D002531:Cerebellum / Q000473:pathology*; D002874:Chromosome Mapping; D004910:Erythrocyte Membrane / Q000502:physiology; D008040:Genetic Linkage; D008565:Membrane Proteins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D011061:Poly A / Q000032:analysis / Q000235:genetics; D011689:Purkinje Cells / Q000473:pathology*; D012313:RNA / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger; D012016:Reference Values; D012156:Reticulocytes / Q000502:physiology; D014158:Transcription, Genetic
D017487:Ankyrins; D001798:Blood Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA