title: zeta-/- Thalassemic mice are affected by two modifying loci and display unanticipated somatic recombination leading to inherited variation.
abstract: Thalassemia is a disease caused by a variety of mutations affecting both the adult and embryonic alpha- and beta-globin loci. A mouse strain carrying an embryonic zeta-globin gene disrupted by the insertion of a PGK-Neo cassette displays an alpha-thalassemia-like syndrome. Embryonic survival of this zeta-null mouse is variable and strongly influenced by genetic background, the 129/SvEv mouse strain displaying a more severe phenotype than C57BL/6. We have identified two modifying loci on C57BL/6 chromosomes 2 and 5, which affect the penetrance of embryonic lethality in the 129/SvEv mouse. Through this work, we were able to observe an interesting effect on somatic recombination events in thalassemic embryos. We show that these events can occur on multiple chromosomes in very early embryonic cells, prior to their allocation to the germline. Our results demonstrate that somatic recombination events can be transmitted to subsequent generations.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Aya
authors.initials: A
authors.lastname: Leder
authors.forename: Jennifer
authors.initials: J
authors.lastname: McMenamin
authors.forename: Karen
authors.initials: K
authors.lastname: Fontaine
authors.forename: Alexander
authors.initials: A
authors.lastname: Bishop
authors.forename: Philip
authors.initials: P
authors.lastname: Leder
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004843:Epistasis, Genetic; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010375:Pedigree; D010641:Phenotype; D011995:Recombination, Genetic; D013789:Thalassemia / Q000235:genetics* / Q000378:metabolism
chemical_list: D005819:Genetic Markers; D005914:Globins