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PubMed2003

Genetic organization of an Acinetobacter baumannii chromosomal region harbouring genes related to siderophore biosynthesis and transport.

The Acinetobacter baumannii 8399 clinical isolate secretes dihydroxybenzoic acid (DHBA) and a high-affinity catechol siderophore, which is different from other bacterial iron chelators already characterized. Complementation assays with enterobactin-deficient Escherichia coli strains led to the isolation of a cosmid clone containing A. baumannii 8399 genes required for the biosynthesis and activation of DHBA. Accordingly, the cloned fragment harbours a dhbACEB polycistronic operon encoding predicted proteins highly similar to several bacterial proteins required for DHBA biosynthesis from chorismic acid. Genes encoding deduced proteins related to the E. coli Fes and the Bacillus subtilis DhbF proteins, and a putative Yersinia pestis phosphopantetheinyl transferase, all of them involved in the assembly and utilization of catechol siderophores in other bacteria, were found next to the dhbACEB locus. This A. baumannii 8399 gene cluster also contained the om73, p45 and p114 predicted genes encoding proteins potentially involved in transport of ferric siderophore complexes. The deduced products of the p114 and p45 genes are putative membrane proteins that belong to the RND and MFS efflux pump proteins, respectively. Interestingly, P45 is highly related to the E. coli P43 (EntS) protein that participates in the secretion of enterobactin. Although P114 is similar to other bacterial efflux pump proteins involved in antibiotic resistance, its genetic arrangement within this A. baumannii 8399 locus is different from that described in other bacteria. The product of om73 is a Fur- and iron-regulated surface-exposed outer-membrane protein. These characteristics together with the presence of a predicted TonB box and its high similarity to other siderophore receptors indicate that OM73 plays such a role in A. baumannii 8399. The 184 nt om73-p114 intergenic region contains promoter elements that could drive the expression of these divergently transcribed genes, all of which are in close proximity to almost perfect Fur boxes. This arrangement explains the iron- and Fur-regulated expression of om73, and provides strong evidence for a similar regulation for the expression of p114.

Acinetobacter baumannii↗
PubMed1997

The 5'-flanking region of the ovarian promoter of the bovine CYP19 gene contains a deletion in a cyclic adenosine 3',5'-monophosphate-like responsive sequence.

Conversion of C19 steroids to estrogens is catalyzed by aromatase P450 (P450arom; the product of the CYP19 gene). In the ovary, P450arom is expressed in granulosa cells of both human (h) and bovine (b) follicles. After the ovulatory surge of gonadotropins, however, P450arom expression is maintained only in the luteinized granulosa cells of the human ovary and is absent from the bovine corpus luteum. We compared the regulation of expression of the ovary-specific human CYP19 (hCYP19ov) and the bovine CYP19 (bCYP19ov) gene by cAMP (forskolin) and sought to determine whether the divergence in the expression of P450arom with the onset of luteinization could be explained by specific cis-acting elements present uniquely in the 5'-flanking DNA of the hCYP19ov or bCYP19ov gene. We, therefore, subcloned DNA encompassing the promoters and 5'-flanking regions of the hCYP19ov or bCYP19ov gene into a promoterless luciferase vector. These constructs were transfected into luteinized bovine granulosa cells or bovine luteal cells in primary culture. Neither cell type exhibits endogenous expression of bovine P450arom. After transfection, cells were treated with either vehicle or 25 microM forskolin. There was little or no increase in luciferase activity after forskolin treatment in cells transfected with any of the bCYP19ov constructs, whereas all of the corresponding hCYP19ov constructs (-693/-16 to -214/-16 bp) expressed reporter activity in the presence of forskolin. This dramatic difference between the activities of the constructs of the two species occurred despite the fact that there is an 88% sequence identity between the bovine and human promoters in the region between -214 to -16 bp. One possible explanation for this variability may be that the bCYP19ov gene has a 1-bp deletion in a cAMP-response element-like sequence (CLS) present at -208 to -201 bp in the hCYP19ov gene that we have shown to be critical for cAMP-stimulated transcription of hCYP19ov in the ovary. When this region of the bCYP19ov promoter was mutated to the hCLS, a partial restoration in luciferase activity was observed after forskolin treatment. Therefore, these results suggest that another sequence in this -214 bp region of the bCYP19ov gene is also contributing to the lack of expression of P450arom after luteinization in the bovine ovary. This lack of expression of the bCYP19ov gene may be due to the presence of a repressive trans-acting factor expressed with the onset of luteinization of the bovine granulosa cell. These results further suggest that in the cow, elements upstream of those employed by the hCYP19ov gene may have been recruited to facilitate regulated expression of the bCYP19ov gene in the absence of a functional CLS.

Animals↗
PubMed1998

Cardiac protein kinase C expression in two models of cardiac hypertrophy associated with an activated cardiac renin-angiotensin system: effects of experimental hyperthyroidism and genetic hypertension (the mRen-2 rat).

There is evidence for a role of protein kinase C (PKC) in the development of cardiac hypertrophy. We examined the expression of individual PKC isoforms in the adult rat heart in two distinct, well-characterised in vivo models of cardiac hypertrophy associated with an activated cardiac renin-angiotensin system, namely experimental hyperthyroidism and the TGR(mRen2)27 rat. The cardiac expression of a range of PKC isoforms (PKC-alpha, PKC-omega, PKC-epsilon, PKC-gamma, and PKC-tau) was examined by immuno-blotting. Our work demonstrates that the expression of total cardiac nPKC-omega and nPKC-epsilon relative to protein is selectively and differentially modified in these models. A consistent up-regulation of nPKC-omega in conjunction with overall down-regulation of nPKC-epsilon was observed in both models. The expression of other PKC isoforms was unaffected. The divergent responses of the expression of the two nPKC isoforms to an activated cardiac renin-angiotensin system in vivo in adulthood suggest that these individual nPKC isoforms subserve specific roles in the response.

Animals↗
PubMed1995

Differential expression of SNAP-25 protein isoforms during divergent vesicle fusion events of neural development.

The presynaptic plasma membrane protein SNAP-25 (synaptosome-associated protein of 25 kDa) has been implicated as one of several neural-specific components that direct constitutive fusion mechanisms to the regulated vesicle trafficking and exocytosis of neurotransmitter release. There exist two alternatively spliced isoforms of SNAP-25, a and b, which differ in a putative membrane-interacting domain. We show that these two isoforms have distinct quantitative and anatomical patterns of expression during brain development, in neurons, and in neuroendocrine cells and that the proteins localize differently in neurites of transfected PC12 pheochromocytoma cells. These findings indicate that alternative isoforms of SNAP-25 may play distinct roles in vesicular fusion events required for membrane addition during axonal outgrowth and for release of neuromodulatory peptides and neurotransmitters.

Adrenal Glands↗
PubMed1999

cDNA cloning, expression and chromosomal localization of two human lysophosphatidic acid acyltransferases.

In this report we describe a pair of human LPAAT isozymes. These isozymes are encoded by distinct genes located on different chromosomes, but share sequence homology, substrate specificity, and intracellular location. The biological value of maintaining the two closely related LPAAT genes in the human genome is not clear. We find that both isozymes are widely expressed, although expression levels do diverge significantly in tissues such as the liver, placenta, testes, and pancreas. We also find that, at least in the artificial system of over-expression in COS7 cells, both isozymes localize to the ER membrane. Thus, distinct tissue-specific or subcellular compartment-specific roles for the two isozymes are not supported by the current experimental evidence. It does remain possible that induction of expression or subcellular translocation of one or the other isozyme may distinguish their functions. A survey of a limited number of acyl CoA substrates indicates that the two isozymes display similar substrate specificities, although slight differences are suggested by the data. However, extensive analysis of both isozymes with multiple substrates in the same assay system will be required to detect physiologically relevant differences in substrate specificity. LPA and PA are central intermediates in phospholipid biogenesis. Furthermore, they have the capacity to mediate signaling both between and within cells. The importance of these mediators is reflected in the growing body of literature dedicated to unraveling the mechanistic basis for their actions. Until recently, the field has been hampered by a dearth of reagents appropriate for the molecular dissection of the LPA and PA metabolic and signaling pathways in eukaryotes. However, the recent cloning of possible LPA receptors will promote further understanding of LPA signaling. Similarly, the recent appearance of LPAAT homologs in the EST database has prompted a flurry of reports describing their characterization. These clones will afford opportunity for defining the function of LPAAT in eukaryotic phospholipid metabolism.

Acyltransferases↗
PubMed2026

Evolutionary Conservation and Reproductive Expression of ABC Transporter Genes in Two Sphenomorphus Skinks.

ATP-binding cassette (ABC) transporters represent one of the largest membrane protein superfamilies in vertebrates, playing essential roles in translocating diverse substrates across membranes. However, knowledge of ABC transporter genes in reptiles remains limited. In this study, we conducted a comprehensive genome-wide identification and characterization of the ABC gene family in oviparous Sphenomorphus incognitus and viviparous Sphenomorphus indicus. A total of 45 ABC genes were identified in each species and classified into seven subfamilies (ABCA-ABCG). Comparative and phylogenetic analyses revealed a generally conserved gene repertoire, with limited duplication events observed mainly in the ABCA and ABCG subfamilies, whereas other subfamilies (e.g., ABCE, ABCF, and ABCD) remained highly conserved. Interestingly, a lineage-specific duplication of ABCC2 was identified in lizards. Oviductal expression profiling revealed distinct temporal patterns of ABC gene expression across reproductive stages. Several genes, including ABCG1, ABCC3, and ABCD4, exhibited conserved expression trajectories across both species, suggesting shared transcriptional regulation. In contrast, ABCA1, ABCB1, and ABCG2 showed species-specific expression patterns, indicating regulatory divergence between the two lizard species. Overall, ABC gene expression was more dynamic in S. incognitus than in S. indicus. In summary, although the ABC transporter family is structurally conserved, it exhibits lineage-specific evolutionary changes and divergent transcriptional regulation in lizard oviducts. This study provides a foundation for understanding the diversity and regulation of ABC transporter genes in reptiles.

Animals↗
PubMed1988

Opposite effects of adenosine on two types of cAMP-induced gene expression in Dictyostelium indicate the involvement of at least two different intracellular pathways for the transduction of cAMP signals.

Adenosine promotes the cAMP-induced increase of mRNAs, probed with the cDNAs D11 and D14, which are preferentially expressed in prestalk cells, while it inhibits cAMP-induced prespore gene expression. Half-maximal inhibition of prespore gene expression occurs at about 300 muM, while prestalk stimulation by adenosine occurs at about 100-fold lower concentrations and requires the presence of cAMP. These results indicate that adenosine interferes with the transduction to cAMP to gene expression and suggest the involvement of two different adenosine target sites. Our data furthermore indicate that the transduction of extracellular cAMP to prespore gene or prestalk gene expression occurs via divergent pathways.

Adenosine↗
PubMed2006

Distant HNF1 site as a master control for the human class I alcohol dehydrogenase gene expression.

Gene duplication and divergence have contributed to the biochemical diversity of the alcohol dehydrogenase (ADH) family. Class I ADH is the major enzyme that catalyzes alcohol to acetaldehyde in the liver. To investigate the mechanism(s) controlling tissue-specific and temporal regulation of the three human class I ADH genes (ADH1A, ADH1B, and ADH1C), we compared genomic sequences for the human and mouse ADH loci and analyzed human ADH gene expression in BAC transgenic mice carrying different lengths of the upstream sequences of the class I ADH. A conserved noncoding sequence, located between the class I and class IV ADH (ADH7) genes, was found to be essential for directing class I ADH gene expression in fetal and adult livers. Within this region, a 275-bp fragment displaying liver-specific DNase I hypersensitivity was bound by HNF1. The HNF1-containing upstream sequence enhanced all three class I ADH promoters in an orientation-dependent manner, and the transcriptional activation depended on binding to the HNF1 site. Deletion of the conserved HNF1 site in the BAC led to the shutdown of human class I ADH gene expression in the transgenic livers, leaving ADH1C gene expression in the stomach unchanged. Moreover, interaction between the upstream element and the class I ADH gene promoters was demonstrated by chromosome conformation capture, suggesting a DNA looping mechanism is involved in gene activation. Taken together, our data indicate that HNF1 binding, at approximately 51 kb upstream, plays a master role in controlling human class I ADH gene expression and may govern alcohol metabolism in the liver.

Alcohol Dehydrogenase↗
PubMed1998

Evolution, organization, and expression of alpha-tubulin genes in the antarctic fish Notothenia coriiceps. Adaptive expansion of a gene family by recent gene duplication, inversion, and divergence.

To assess the organization and expression of tubulin genes in ectothermic vertebrates, we have chosen the Antarctic yellowbelly rockcod, Notothenia coriiceps, as a model system. The genome of N. coriiceps contains approximately 15 distinct DNA fragments complementary to alpha-tubulin cDNA probes, which suggests that the alpha-tubulins of this cold-adapted fish are encoded by a substantial multigene family. From an N. coriiceps testicular DNA library, we isolated a 13.8-kilobase pair genomic clone that contains a tightly linked cluster of three alpha-tubulin genes, designated NcGTbalphaa, NcGTbalphab, and NcGTbalphac. Two of these genes, NcGTbalphaa and NcGTbalphab, are linked in head-to-head (5' to 5') orientation with approximately 500 bp separating their start codons, whereas NcGTbalphaa and NcGTbalphac are linked tail-to-tail (3' to 3') with approximately 2.5 kilobase pairs between their stop codons. The exons, introns, and untranslated regions of the three alpha-tubulin genes are strikingly similar in sequence, and the intergenic region between the alphaa and alphab genes is significantly palindromic. Thus, this cluster probably evolved by duplication, inversion, and divergence of a common ancestral alpha-tubulin gene. Expression of the NcGTbalphac gene is cosmopolitan, with its mRNA most abundant in hematopoietic, neural, and testicular tissues, whereas NcGTbalphaa and NcGTbalphab transcripts accumulate primarily in brain. The differential expression of the three genes is consistent with distinct suites of putative promoter and enhancer elements. We propose that cold adaptation of the microtubule system of Antarctic fishes is based in part on expansion of the alpha- and beta-tubulin gene families to ensure efficient synthesis of tubulin polypeptides.

Amino Acid Sequence↗
PubMed1999

Na(+)/H(+) exchangers (NHE1-3) have similar turnover numbers but different percentages on the cell surface.

NHE1, NHE2, and NHE3 are well-characterized cloned members of the mammalian Na(+)/H(+) exchanger (NHE) gene family. Given the specialized function and regulation of NHE1, NHE2, and NHE3, we compared basal turnover numbers of NHE1, NHE2, and NHE3 measured in the same cell system: PS120 fibroblasts lacking endogenous NHEs. NHE1, NHE2, and NHE3 were epitope tagged with vesicular stomatitis virus glycoprotein (VSVG). The following characteristics were determined on the same passage of cells transfected with NHE1V, NHE2V, or NHE3V: 1) maximal reaction velocity (V(max)) by (22)Na(+) uptake and fluorometery, 2) total amount of NHE protein by quantitative Western analysis with internal standards of VSVG-tagged maltose-binding protein, and 3) cell surface expression by cell surface biotinylation. Cell surface expression (percentage of total NHE) was 88.8 +/- 3.5, 64.6 +/- 3.3, 20.0 +/- 2.6, and 14.0 +/- 1.3 for NHE1V, 85- and 75-kDa NHE2V, and NHE3V, respectively. Despite these divergent cell surface expression levels, turnover numbers for NHE1, NHE2, and NHE3 were similar (80.3 +/- 9.6, 92.1 +/- 8.6, and 99.2 +/- 9.1 s(-1), when V(max) was determined using (22)Na uptake at 22 degrees C and 742 +/- 47, 459 +/- 16, and 609 +/- 39 s(-1) when V(max) was determined using fluorometry at 37 degrees C). These data indicate that, in the same cell system, intrinsic properties that determine turnover number are conserved among NHE1, NHE2, and NHE3.

Animals↗
PubMed1999

Highly divergent lentiviral Tat proteins activate viral gene expression by a common mechanism.

The human immunodeficiency virus type 1 (HIV-1) Tat protein (hTat) activates transcription initiated at the viral long terminal repeat (LTR) promoter by a unique mechanism requiring recruitment of the human cyclin T1 (hCycT1) cofactor to the viral TAR RNA target element. While activation of equine infectious anemia virus (EIAV) gene expression by the EIAV Tat (eTat) protein appears similar in that the target element is a promoter proximal RNA, eTat shows little sequence homology to hTat, does not activate the HIV-1 LTR, and is not active in human cells that effectively support hTat function. To address whether eTat and hTat utilize similar or distinct mechanisms of action, we have cloned the equine homolog of hCycT1 (eCycT1) and examined whether it is required to mediate eTat function. Here, we report that expression of eCycT1 in human cells fully rescues eTat function and that eCycT1 and eTat form a protein complex that specifically binds to the EIAV, but not the HIV-1, TAR element. While hCycT1 is also shown to interact with eTat, the lack of eTat function in human cells is explained by the failure of the resultant protein complex to bind to EIAV TAR. Critical sequences in eCycT1 required to support eTat function are located very close to the amino terminus, i.e., distal to the HIV-1 Tat-TAR interaction motif previously identified in the hCycT1 protein. Together, these data provide a molecular explanation for the species tropism displayed by eTat and demonstrate that highly divergent lentiviral Tat proteins activate transcription from their cognate LTR promoters by essentially identical mechanisms.

Amino Acid Sequence↗
PubMed2001

Gene and cluster-specific expression of the Iroquois family members during mouse development.

Mammalian homologues of the Drosophila Iroquois homeobox gene complex, involved in patterning and regionalization of differentiation, have recently been identified (Mech. Dev., 69 (1997) 169; Dev. Biol., 217 (2000) 266; Dev. Dyn., 218 (2000) 160; Mech. Dev., 91 (2000) 317; Dev. Biol., 224 (2000) 263; Genome Res., 10 (2000) 1453; Mech. Dev., 103 (2001) 193). The six members of the murine family were found to be organized in two cognate clusters of three genes each, Irx1, -2, -4 and Irx3, -5, -6, respectively (Peters et al., 2000). As a basis for further study of their regulation and function we performed a comparative analysis of the genomic organization and of the expression patterns of all six Irx genes. The genes are expressed in highly specific and regionalized patterns of ectoderm, mesoderm and endoderm derived tissues. In most tissues the pattern of expression of the clustered genes, especially of Irx1 and -2 and of Irx3 and -5, respectively, closely resembled each other while those of Irx4 and -6 were very divergent. Interestingly, the expression of cognate genes was found to be mutually exclusive in adjacent and interacting tissues of limb, heart and the laryncho-pharyncheal region. The results indicate that the Irx genes are coordinately regulated at the level of the cluster.

Animals↗
PubMed2005

Expression of Hex during feather bud development.

We studied proline-rich divergent homeobox gene Hex/Prh expression in the dorsal skin of chick embryo during feather bud development. Hex mRNA expression was first observed in the dorsolateral ectoderm and mesenchyme at 5 days, then in the epithelium and the dermis of the dorsal skin before placode (primordium of feather bud) formation and then was restricted to the placode and the dermis under the placode. Afterward, Hex expression was seen in the epidermis and the dermis of the posterior region of short bud. In accordance with Hex mRNA expression in the placode, Hex protein was observed in the epidermis as well as in the dermis of the placode. Immunoelectron microscopic study indicated that the protein located both in the nuclei and cytoplasm of the epidermis and the dermis at the short bud stage. The Wnt signaling pathway plays an essential role in the early inductive events in hair (Wnt3a and 7a) and feather (Wnt7a) follicles. The pattern of Hex expression in the epidermis was similar to that of Wnt7a, while little, if any, expression of Wnt7a was detected in the dermis under the placode or the dermis of the short bud compared with that of Hex, suggesting that Hex plays an important role in the initiation of feather morphogenesis.

Animals↗
PubMed1987

Expression of transfected vimentin genes in differentiating murine erythroleukemia cells reveals divergent cis-acting regulation of avian and mammalian vimentin sequences.

We studied the expression of transfected chicken and hamster vimentin genes in murine erythroleukemia (MEL) cells. MEL cells normally repress the levels of endogenous mouse vimentin mRNA during inducermediated differentiation, resulting in a subsequent loss of vimentin filaments. Expression of vimentin in differentiating MEL cells reflects the disappearance of vimentin filaments during mammalian erythropoiesis in vivo. In contrast, chicken erythroid cells express high levels of vimentin mRNA and vimentin filaments during terminal differentiation. We demonstrate here that chicken vimentin mRNA levels increase significantly in differentiating transfected MEL cells, whereas similarly transfected hamster vimentin genes are negatively regulated. In conjunction with in vitro nuclear run-on transcription experiments, these results suggest that the difference in vimentin expression in avian and mammalian erythropoiesis is due to a divergence of cis-linked vimentin sequences that are responsible for transcriptional and posttranscriptional regulation of vimentin gene expression. Transfected chicken vimentin genes produce functional vimentin protein and stable vimentin filaments during MEL cell differentiation, further demonstrating that the accumulation of vimentin filaments is determined by the abundance of newly synthesized vimentin.

Animals↗
PubMedDate not supplied

Treatment problems of the hospitalized physician.

Treatment problems arise both when the physician or other health care professional must be hospitalized for psychiatric disturbance and, even prior to hospitalization, in the process by which the physician comes to recognize and accept in himself an emotional illness of severe proportions. Hospitalization can represent a severe narcissistic trauma, which entails a radical role reversal (from caretaker to patient) and severely undermines the physician-patient's sense of personal and professional identity. Conflicts around these issues tend to become externalized within the hospital setting up characteristic patterns of conflict within the therapy (between patient and therapist) and within the ward community (between patient and ward staff, as well as between treating physician and ward staff). The expression of these conflicts and patterns of interaction are discussed in two cases-both psychotic and suicidal physicians-who, though the patterns of resistance and externalization took divergent forms, nonetheless expressed the same underlying issues.

Career Choice↗
PubMed1992

A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia.

HB24 is a diverged homeobox gene known to be expressed in hematopoietic progenitor cells. We show here that the inhibition of HB24 expression in CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation of these cells in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides also reduced the levels of c-fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells treated with control oligonucleotides. Conversely, the transient transfection of HB24 into a subpopulation of CD34 cells inhibited their differentiation into mature hematopoietic cell types. In addition, HB24 messenger RNA transcripts were elevated in bone marrow and peripheral blood mononuclear cells isolated from patients with acute myelogenous leukemia compared with normal controls. These data suggest that HB24 is an important transcription factor during hematopoietic progenitor proliferation and that differentiation to specific cell types requires its downregulation. Furthermore, dysregulated expression of HB24 impairs the normal differentiation of hematopoietic progenitors and may contribute to leukemogenesis.

Antigens, CD↗
PubMed2001

The LIM-homeodomain gene family in the developing Xenopus brain: conservation and divergences with the mouse related to the evolution of the forebrain.

A comparative analysis of LIM-homeodomain (LIM-hd) expression patterns in the developing stage 32 Xenopus brain is presented. x-Lhx2, x-Lhx7, and x-Lhx9 were isolated and their expression, together with that of x-Lhx1 and x-Lhx5, was analyzed in terms of prosomeric brain development and LIM-hd combinatorial code and compared with mouse expression data. The results show an almost complete conservation of expression patterns in the diencephalon. The Lhx1/5 and Lhx2/9 subgroups label the pretectum/ventral thalamus/zona limitans versus the dorsal thalamus, respectively, in alternating stripes of expression in both species. Conversely, strong divergences in expression patterns are observed between the telencephalon of the two species for Lhx1/5 and Lhx2/9. Lhx7 exhibits particularly conservative patterns and is proposed as a medial ganglionic eminence marker. The conservation of diencephalic segments is proposed to mirror the conservative nature of diencephalic structures across vertebrates. In contrast, the telencephalic divergences are proposed to reflect the emergence of significant novelty in the telencephalon (connectivity changes) at the anamniote/amniote transition. Moreover, the data allow the new delineation of pallial and subpallial domains in the developing frog telencephalon, which are compared with mouse subdivisions. In the pallium, the mouse combinatorial expression of LIM-hd is notably richer than in the frog, again possibly reflecting evolutionary changes in cortical connectivity.

Animals↗
PubMed1995

Highly conserved 3' UTR and expression pattern of FXR1 points to a divergent gene regulation of FXR1 and FMR1.

A search for genes with sequence homologies to the FMR1 gene resulted in the isolation of mouse and human homologues of the recently described FXR1 gene. The mouse FXR1 gene shares amino acid identity and similarity of 99.1% and 99.6%, respectively, with the human FXR1 gene and amino acid identify and similarity of 67.3% and 79.5% respectively, with the mouse FMR1 gene. The 3' untranslated region of the FXR1 gene is extremely conserved between human and mouse. The gene structure of FXR1 is very similar to that of FMR1 and both genes probably originate from a common ancestral gene. In contrast to the previously published localization, we mapped the transcribed gene to chromosome region 3q28. An intronless form of the FXR1 gene, either processed functional homologue or pseudogene was localized to 12q12. Northern blot analysis of the human FXR1 gene revealed an expression pattern of a housekeeping gene with stronger expression in muscle. RNA in situ hybridization to sections of mouse embryo and adult tissues has shown that during embryonic development the mouse FXR1 mRNA is expressed in different tissues, most prominent in skeletal muscle, the gonads and distinct regions of the central nervous system, and that the expression is restricted to proliferating cells. While FMR1 is highly expressed in proliferating spermatogonia, FXR1 is highly expressed in postmeiotic spermatids.

Amino Acid Sequence↗