TDP-43, a neuro-pathosignature factor, is essential for early mouse embryogenesis.
TDP-43 is a highly conserved and ubiquitously expressed nuclear protein. It has been implicated in the regulation of transcription, alternative splicing, translation, and neuronal plasticity. TDP-43 has also been shown to be a disease signature protein associated with several neurodegenerative diseases including amyotrophic lateral sclerosis. However, the correlation of the physiological functions of TDP-43 with these diseases remains unknown. We have used the gene targeting approach to disrupt the expression of TDP-43 in mouse. Loss of the TDP-43 expression results in peri-implantation lethality of mice between embryonic days (E) 3.5 and 6.5. Blastocysts of the homozygous Tardbp null mutants are morphologically normal, but exhibit defective outgrowth of the inner cell mass in vitro. Our data demonstrate the essential function of TDP-43 in peri-implantation stage during the embryo development, likely because of its involvement in multiple biological processes in a variety of cell types.
Wu
Lien-Szu
LS
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China.
Cheng
Wei-Cheng
WC
Hou
Shin-Chen
SC
Yan
Yu-Ting
YT
Jiang
Si-Tse
ST
Shen
C-K James
CK
D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020043:Genes, Essential; D005838:Genotype; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004268:DNA-Binding Proteins