Human Molecular Genetics Advance Access originally published online on January 13, 2005
Human Molecular Genetics 2005 14(5):615-625; doi:10.1093/hmg/ddi058
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Human Molecular Genetics, Vol. 14, No. 5 © Oxford University Press 2005; all rights reserved
–/– Thalassemic mice are affected by two modifying loci and display unanticipated somatic recombination leading to inherited variation
1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA and 2Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
* To whom correspondence should be addressed. Email: leder{at}gentics.med.harvard.edu
Received November 9, 2004; Revised December 27, 2004; Accepted January 5, 2005
Thalassemia is a disease caused by a variety of mutations affecting both the adult and embryonic 
- and ß-globin loci. A mouse strain carrying an embryonic 
-globin gene disrupted by the insertion of a PGK-Neo cassette displays an -thalassemia-like syndrome. Embryonic survival of this -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.