Hemogloblin Switching inSheepandGoats: Erythropoietin-Dependent Synthesis ofHemoglobin CinGoatBone-Marrow Cultures* (geneswitching/OA globin/carboxymethylcellulose chromatography/blood/anemia)

The anemia-induced switchfromhemo. globin A(cr22A) tohemoglobin C (aZ82C) synthesis occurring invivoinsheepandgoatshasbeenreproduced intissue culture ofgoatbone-marrow cells. Cultivation ofprimary cultures ofgoatbonemarrowinthepresence oferythro- poietin results intheappearance ofdetectable amountsof #cglobin after 48-72hr,aswellasinadecrease inMAglobin. A population ofproerythroblasts, aswellasactive heme andglobin synthesis, aremaintained foratleast 3daysin erythropoietin-treated, but not in erythropoietin-defi- cdent, cultures. Thesefindings demonstrate(i)main- tenanceof erythropoietin-responsive cellsfrombone marrowinvitro, and(ii) switching invitro fromthesyn- thesis ofaglobin chaincodedbyonegenetothatcodedby a different, nonallelic gene.Bone-marrow culture might beauseful modelsystemforstudyofthemechanismof actionoferythropoietin andforstudyoftheactivation (andinactivation) ofspecific genesinvitro. Ineukaryotes, themolecular mechanisms involved ingene activation andinthesubsequent production ofspecific cell proteins arelargely unknown. Tostudygeneactivation in mammals, acell population isneeded thatcanbestimulated totranscribe themessenger RNA foraparticular protein in response toadefined stimulus. Wehavestudied theerythro- poietin-dependent