title: Distinct fetal Ank-1 and Ank-2 related proteins and mRNAs in normal and nb/nb mice.
abstract: Mice homozygous for the mutation normoblastosis (gene symbol nb on chromosome 8) are deficient in erythroid ankyrin (ANK-1) and have a severe hemolytic anemia throughout life. Characteristic of the disease is a dramatic decrease in the level of expression of the Ank-1 gene (chromosome 8). The other major ankyrin transcript, brain ankyrin (Ank-2 on chromosome 3) is expressed at normal levels in nb/nb mice. Surprisingly, nb/nb fetuses have normal erythrocyte counts despite the decreased levels of Ank-1 transcripts. We previously hypothesized that fetal-specific ankyrin-related proteins could exist in nb/nb fetuses to account for the lack of detrimental effects of ANK-1 deficiency. In the present report, Western and Northern blot analyses were performed on hematopoietic cells isolated from nb/nb and +/+ fetuses. An ANK-1-related protein (165 Kd) in fetal reticulocytes persisted in adult nb/nb but not in +/+ reticulocytes. An Ank-1-related transcript of 5.5 kb was found in fetal reticulocytes. This transcript appeared to be upregulated in nb/nb but not in +/+ adult reticulocytes. A fetal-specific ANK-2-related protein (155 Kd) was present in nb/nb and in +/+ fetal reticulocytes. Ank-2-related fetal liver mRNAs were present during the time the liver was actively generating erythrocytes. Neither the Ank-2-related transcripts nor the 155-Kd ANK-2-related protein were found in +/+ or mutant adult reticulocytes. The data indicate that (1) unique ankyrin-related proteins and mRNAs present in fetal erythrocytes may stabilize the ankyrin-deficient nb/nb erythrocytes and (2) adult nb/nb mice may upregulate fetal gene transcripts to compensate for the ANK-1 deficiency.
authors: Jackson Laboratory, Bar Harbor, ME 04609.
authors: L L
authors: LL
authors: Peters
authors: L C
authors: LC
authors: Turtzo
authors: C S
authors: CS
authors: Birkenmeier
authors: J E
authors: JE
authors: Barker
mesh_terms: D000743:Anemia, Hemolytic / Q000097:blood / Q000235:genetics; D000818:Animals; D017487:Ankyrins / Q000097:blood* / Q000235:genetics; D001923:Brain Chemistry; D004912:Erythrocytes / Q000737:chemistry; D005312:Fetal Blood / Q000737:chemistry*; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D015151:Immunoblotting; D008099:Liver / Q000737:chemistry / Q000196:embryology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis / Q000097:blood*; D012156:Reticulocytes / Q000737:chemistry
chemical_list: D017487:Ankyrins; D012333:RNA, Messenger