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Articles

Targeted Deletion of the Gene Encoding the La Autoantigen (Sjögren's Syndrome Antigen B) in B Cells or the Frontal Brain Causes Extensive Tissue Loss

Sergei Gaidamakov, Olga A. Maximova, Hyongi Chon, Nathan H. Blewett, Hongsheng Wang, Amanda K. Crawford, Amanda Day, Natalie Tulchin, Robert J. Crouch, Herbert C. Morse III, Robert D. Blitzer, Richard J. Maraia
Sergei Gaidamakov
aIntramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
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Olga A. Maximova
bLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Hyongi Chon
aIntramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
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Nathan H. Blewett
aIntramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
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Hongsheng Wang
cLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Amanda K. Crawford
aIntramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
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Amanda Day
aIntramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
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Natalie Tulchin
dDepartment of Pathology, Mount Sinai School of Medicine, New York, New York, USA
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Robert J. Crouch
aIntramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
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Herbert C. Morse III
cLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Robert D. Blitzer
eDepartment of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York, USA
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Richard J. Maraia
aIntramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
fCommissioned Corps, U.S. Public Health Service, Washington, DC, USA
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DOI: 10.1128/MCB.01010-13
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ABSTRACT

La antigen (Sjögren's syndrome antigen B) is a phosphoprotein associated with nascent precursor tRNAs and other RNAs, and it is targeted by autoantibodies in patients with Sjögren's syndrome, systemic lupus erythematosus, and neonatal lupus. Increased levels of La are associated with leukemias and other cancers, and various viruses usurp La to promote their replication. Yeast cells (Saccharomyces cerevisiae and Schizosaccharomyces pombe) genetically depleted of La grow and proliferate, whereas deletion from mice causes early embryonic lethality, raising the question of whether La is required by mammalian cells generally or only to surpass a developmental stage. We developed a conditional La allele and used it in mice that express Cre recombinase in either B cell progenitors or the forebrain. B cell Mb1Cre La-deleted mice produce no B cells. Consistent with αCamKII Cre, which induces deletion in hippocampal CA1 cells in the third postnatal week and later throughout the neocortex, brains develop normally in La-deleted mice until ∼5 weeks and then lose a large amount of forebrain cells and mass, with evidence of altered pre-tRNA processing. The data indicate that La is required not only in proliferating cells but also in nondividing postmitotic cells. Thus, La is essential in different cell types and required for normal development of various tissue types.

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Targeted Deletion of the Gene Encoding the La Autoantigen (Sjögren's Syndrome Antigen B) in B Cells or the Frontal Brain Causes Extensive Tissue Loss
Sergei Gaidamakov, Olga A. Maximova, Hyongi Chon, Nathan H. Blewett, Hongsheng Wang, Amanda K. Crawford, Amanda Day, Natalie Tulchin, Robert J. Crouch, Herbert C. Morse III, Robert D. Blitzer, Richard J. Maraia
Molecular and Cellular Biology Dec 2013, 34 (1) 123-131; DOI: 10.1128/MCB.01010-13

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Targeted Deletion of the Gene Encoding the La Autoantigen (Sjögren's Syndrome Antigen B) in B Cells or the Frontal Brain Causes Extensive Tissue Loss
Sergei Gaidamakov, Olga A. Maximova, Hyongi Chon, Nathan H. Blewett, Hongsheng Wang, Amanda K. Crawford, Amanda Day, Natalie Tulchin, Robert J. Crouch, Herbert C. Morse III, Robert D. Blitzer, Richard J. Maraia
Molecular and Cellular Biology Dec 2013, 34 (1) 123-131; DOI: 10.1128/MCB.01010-13
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