ζ-/-thalassemic mice are affected by two modifying loci and display unanticipated somatic recombination leading to inherited variation

Aya Leder, Jennifer McMenamin, Karen Fontaine, Alexander Bishop, Philip Leder

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Thalassemia is a disease caused by a variety of mutations affecting both the adult and embryonic α- and β-globin loci. A mouse strain carrying an embryonic ζ-globin gene disrupted by the insertion of a PGK-Neo cassette displays an α-thalassemia-like syndrome. Embryonic survival of this ζ-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.

Original languageEnglish (US)
Pages (from-to)615-625
Number of pages11
JournalHuman molecular genetics
Volume14
Issue number5
DOIs
StatePublished - Mar 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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