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Molecular and Cellular Biology, November 2006, p. 8410-8417, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.01196-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cold Shock Domain Family Members YB-1 and MSY4 Share Essential Functions during Murine Embryogenesis{triangledown} ,{dagger}

Zhi Hong Lu, Jason T. Books, and Timothy J. Ley*

Division of Oncology, Departments of Medicine and Genetics, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63110

Received 30 June 2006/ Returned for modification 28 July 2006/ Accepted 27 August 2006

Three cold shock domain (CSD) family members (YB-1, MSY2, and MSY4) exist in vertebrate species ranging from frogs to humans. YB-1 is expressed throughout embryogenesis and is ubiquitously expressed in adult animals; it protects cells from senescence during periods of proliferative stress. YB-1-deficient embryos die unexpectedly late in embryogenesis (embryonic day 18.5 [E18.5] to postnatal day 1) with a runting phenotype. We have now determined that MSY4, but not MSY2, is also expressed during embryogenesis; its abundance declines substantially from E9.5 to E17.5 and is undetectable on postnatal day 1(adult mice express MSY4 in testes only). Whole-mount analysis revealed similar patterns of YB-1 and MSY4 RNA expression in E11.5 embryos. To determine whether MSY4 delays the death of YB-1-deficient embryos, we created and analyzed MSY4-deficient mice and then generated YB-1 and MSY4 double-knockout embryos. MSY4 is dispensable for normal development and survival, but the testes of adult mice have excessive spermatocyte apoptosis and seminiferous tubule degeneration. Embryos doubly deficient for YB-1 and MSY4 are severely runted and die much earlier (E8.5 to E11.5) than YB-1-deficient embryos, suggesting that MSY4 indeed shares critical cellular functions with YB-1 in the embryonic tissues where they are coexpressed.

* Corresponding author. Mailing address: Division of Oncology, Section of Stem Cell Biology, Campus Box 8007, 660 South Euclid Ave., St. Louis, MO 63110-1093. Phone: (314) 362-8831. Fax: (314) 362-9333. E-mail: tley{at}im.wustl.edu.

{triangledown} Published ahead of print on 5 September 2006.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, November 2006, p. 8410-8417, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.01196-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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