Abstract
Although the conditional gene knockout (KO) is a better choice for observing its phenotype in a specific cell, tissue, and/or organ, the simple null gene KO could nevertheless be attempted initially to scan its overall phenotypes at the level of the whole-body system, especially for a new gene such as Crlz-1. Therefore, with a hope to glean phenotypic clues for Crlz-1 at the whole-body system, we attempted to generate its null KO mice. Contrary to our original desire, Crlz-1 homozygous null KO mice were not born. However, in the chasing of their homozygous KO embryos, they were found to be lethally impaired from early development, remaining in a state of small globular mass without ever leading to a body shape, indicating the critical role of Crlz-1 as a Wnt target gene for the proliferation and/or differentiation of cells during early mouse embryonic development.
Highlights
Crlz-1, called Utp3 (U three protein 3) as is involved in the processing of rRNA by the small subunit processome (SSU) [1], was first reported as Sas10 with its protein’s transcriptional derepression activity in yeast [2], and was later cloned by its protein’s ability to bind CBFβ in the mice [3]
Mice, because the Wnt signal is reported to be involved in the proliferation and/or differentiation of cells during embryogenesis [19–22], and Runx/CBFβ is known to be essential for the early embryonic hematopoiesis [23–25] and osteogenesis [26]
The transcriptional derepression activity of Sas10 on the silenced chromatin, which was demonstrated by its overexpression in Saccharomyces cerevisiae [2], might potentially be explained in a way similar to the molecular working mechanism of Crlz-1 as described above in mouse and/or human cells
Summary
Crlz-1 (charged amino acid-rich leucine zipper-1), called Utp (U three protein 3) as is involved in the processing of rRNA by the small subunit processome (SSU) [1], was first reported as Sas (something about silencing 10) with its protein’s transcriptional derepression activity in yeast [2], and was later cloned by its protein’s ability to bind CBFβ (core binding factor β) in the mice [3]. In accordance with its original cloning by CBFβ as a bait of yeast two-hybrid screen [3], Crlz-1 was demonstrated to work by mobilizing the cytoplasmic CBFβ into nucleus to allow its heterodimerization with Runx (runt-related transcription factor), and thereby to form a higher affinity form of Runx/CBFβ heterodimer in both pre-B and GC centroblast cells [9,10,12]. When we chased for its homozygous KO embryos after sacrificing their pregnant mice at various days post coitum (dpc), we did detect Crlz-1 homozygous KO embryos that were lethally impaired from their early development as compared to their wild-type and heterozygous KO littermates, potentially indicating the critical role of Crlz-1 for the proliferation and/or differentiation of cells during embryogenesis
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