The nifk gene is widely expressed in mouse tissues and is up-regulated in denervated hind limb muscle

Denervation of skeletal muscle alters the expression of many genes, which may be important for establishing optimal conditions for reinnervation. Using the differential display technique we have attempted to discover neurally regulated genes in skeletal muscle. An mRNA that is up-regulated in denervated hind limb muscle was identified and cloned. The cDNA encodes an RNA-binding protein, which was discovered during the course of this work to be a nucleolar protein interacting with the fork-head associated domain of the proliferation marker protein Ki-67, and named NIFK. We show that the nifk gene is widely expressed in adult mouse tissues and that the expression is up-regulated in denervated hind limb muscle. No difference between expression in perisynaptic and extrasynaptic portions of muscle was observed. The widespread expression in adult tissues suggests that the NIFK protein has other functions in addition to its interaction with Ki-67, which is only expressed in proliferating cells.     

LRIG1 protein in human cells and tissues

We have recently cloned the human LRIG1 gene (formerly LIG1). LRIG1 is a predicted integral cell-surface protein showing similarities to Kekkon-1, the Drosophila melanogaster epidermal growth-factor-receptor antagonist. A specific peptide antibody, LRIG1-151, was raised in rabbits and used to study the LRIG1 protein. LRIG1 migrated in denaturing polyacrylamide gel electrophoresis under reducing conditions as two species with apparent molecular weights of 143 kDa and 134 kDa, and as two fragments corresponding to an N-terminal 111-kDa species and a C-terminal 32-kDa species. Under non-reducing conditions, both apparent monomers and apparent higher molecular weight complexes were evident. Immunoblotting analysis of cell-surface-biotinylated lysates and confocal microscopy revealed that LRIG1 was localized to the cell surface in ZR-75 cells expressing endogenous LRIG1 and in COS-7 cells expressing a synthetic LRIG1-GFP fusion protein. Immunohistochemical analysis of normal human tissues showed staining for LRIG1 in epithelia in various organs, scattered neurons, and muscles. Immunoblotting demonstrated LRIG1 protein in tissue lysates from normal human prostate, mammary epithelial cells, ileum, stomach, lung, and cerebral cortex. These results demonstrate that LRIG1 is an integral cell-surface membrane protein that is expressed by specific cells in various human tissues and that its 143-kDa form might be cleaved into 111-kDa and 32-kDa fragments.     

The chicken alpha 1 (XI) collagen gene is widely expressed in embryonic tissues.

Complementary DNA and genomic DNA clones corresponding to the chicken alpha 1 (XI) collagen gene were isolated and characterized. These recombinant DNA clones covered 2667 base pairs of the mRNA and encode 624 amino acids of the triple helical region plus the entire carboxyl-terminal propeptide. Northern blot analysis showed a major band of approximately 6.5 kilobases and a minor band of approximately 7.5 kilobases. A combination of Northern blot and in situ hybridization analyses showed that, in addition to its presence in cartilage, this mRNA also is present in a wide variety of chicken noncartilaginous embryonic tissues including brain, heart, skeletal muscle, calvaria, and skin, but was not detected in liver. Type II collagen mRNA has also been detected at low levels in these same tissues. Also, similar to the mRNA for the alpha 1 chain for type II collagen, the alpha 1 (XI) collagen mRNA is detected in limb mesenchyme prior to condensation and differentiation of the core mesenchyme into cartilage.     

The EGF-CFC gene family in vertebrate development

EGF-CFC genes encode extracellular proteins that play key roles in intercellular signaling pathways during vertebrate embryogenesis. Mutations in zebrafish and mouse EGF-CFC genes lead to defects in germ-layer formation, anterior-posterior axis orientation and left-right axis specification. In addition, members of the EGF-CFC family have been implicated in carcinogenesis. Although formerly regarded as signaling molecules that are distant relatives of epidermal growth factor (EGF), recent findings indicate that EGF-CFC proteins act as essential cofactors for Nodal, a member of the transforming growth factor beta (TGF-beta) family. Here, we review molecular genetic evidence from mouse and zebrafish on biological and biochemical roles of the EGF-CFC family, and discuss differing models for EGF-CFC protein function.     

BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice

BOK/MTD was discovered as a protein that binds to the anti-apoptotic Bcl-2 family member MCL-1 and shares extensive amino-acid sequence similarity to BAX and BAK, which are essential for the effector phase of apoptosis. Therefore, and on the basis of its reported expression pattern, BOK is thought to function in a BAX/BAK-like pro-apoptotic manner in female reproductive tissues. In order to determine the function of BOK, we examined its expression in diverse tissues and investigated the consequences of its loss in Bok(-/-) mice. We confirmed that Bok mRNA is prominently expressed in the ovaries and uterus, but also observed that it is present at readily detectable levels in several other tissues such as the brain and myeloid cells. Bok(-/-) mice were produced at the expected Mendelian ratio, appeared outwardly normal and proved fertile. Histological examination revealed that major organs in Bok(-/-) mice displayed no morphological aberrations. Although several human cancers have somatically acquired copy number loss of the Bok gene and BOK is expressed in B lymphoid cells, we found that its deficiency did not accelerate lymphoma development in Eμ-Myc transgenic mice. Collectively, these results indicate that Bok may have a role that largely overlaps with that of other members of the Bcl-2 family, or may have a function restricted to specific stress stimuli and/or tissues.     

Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues

Vertebrates possess multiple respiratory globins that differ in terms of structure, function, and tissue distribution. Three types of globins have been described so far: hemoglobin facilitates the transport of oxygen in the blood, myoglobin serves oxygen transport and storage in the muscle, and neuroglobin has a yet unidentified function in nerve cells. Here we report the identification of a fourth and novel type of globin in mouse, man, and zebrafish. It is expressed in apparently all types of human tissue and therefore has been called cytoglobin (CYGB). Mouse and human CYGBs comprise 190 amino acids; the zebrafish CYGB, 174 amino acids. The human CYGB gene is located on chromosome 17q25. The mammalian genes display a unique exon-intron pattern with an additional exon resulting in a C-terminal extension of the protein, which is absent in the fish CYGB. Phylogenetic analyses suggest that the CYGBs had a common ancestor with vertebrate myoglobins. This indicates that the vertebrate myoglobins are in fact a specialized intracellular globin that evolved in adaptation to the special needs of muscle cells.     

All three human ras genes are expressed in a wide range of tissues

We examined the expression of the ras gene family (Ha-ras, Ki-ras, N-ras) in human fetal tissues (14 week) and in several human tumor cell lines. Dot blot hybridization showed that the three ras genes were expressed in all of the samples analysed, with a range of expression between 10 and 180 molecules/cell. There was no correlation between levels of expression of ras genes and the type of ras gene activated in different tumor types.     

The similarity of gene expression between human and mouse tissues

Meta-analysis of human and mouse microarray data reveals conservation of patterns of gene expression that will help to better characterize the evolution of gene expression.     

The mouse has a Polycomb-like chromobox gene.

The Drosophila gene Polycomb (Pc) has been implicated in the clonal inheritance of determined states and is a trans-regulator of the Antennapedia-like homeobox genes. Pc shares a region of homology (the chromobox) with the Drosophila gene Heterochromatin Protein 1 (HP1), a component of heterochromatin. The Pc chromobox has been used to isolate a mouse chromobox gene, M33, which encodes a predicted 519 amino acid protein. The M33 chromodomain is more similar to that in the Pc protein, than that in the HP1 protein. In addition to the chromodomain, the M33 and Pc proteins also share a region of homology at their C termini. The temporal and spatial expression patterns of M33 have been studied by in situ hybridization and northern analysis. During the final 10 days of embryonic development, M33 expression mirrors that of the cell-cycle-specific cyclin B gene. It is therefore suggested that the rate of cellular proliferation controls M33 expression. From comparisons of the characteristics of M33 with those of Pc it is proposed that M33 is a Pc-like chromobox gene. The roles of M33 and Pc in models of cellular memory are examined and implications of the memory models addressed.