Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tendon-Specific Dicer Deficient Mice Exhibit Hypoplastic Tendon Through the Downregulation of Tendon-Related Genes and MicroRNAs.

ABSTRACT: Tendon is a fibrous connective tissue, that is, transmitting the forces that permit body movement. However, tendon/ligament biology is still not fully understood and especially, the role of miRNAs in tendon/ligament is sparse and uncharacterized in in vivo models. The objectives of this study were to address the function of DICER using mice with tendon/ligament-specific deletion of Dicer (Dicer conditional knockout; cKO), and to identify key miRNAs in tendon/ligament. Dicer cKO mice exhibited hypoplastic tendons through structurally abnormal collagen fibrils with downregulation of tendon-related genes. The fragility of tendon did not significantly affect the tensile strength of tendon in Dicer cKO mice, but they showed larger dorsiflexion angle in gait compared with Control mice. We identified two miRNAs, miR-135a and miR-1247, which were highly expressed in the Achilles tendon of Control mice and were downregulated in the Achilles tendon of Dicer cKO mice compared with Control mice. miR-135a mimic increased the expression of tendon-related genes in injured Achilles tendon-derived fibroblasts. In this study, Dicer cKO mice exhibited immature tendons in which collagen fibrils have small diameter with the downregulation of tendon-related genes such as transcriptional factor, extracellular matrix, and miRNAs. Thus, DICER plays an important role in tendon maturation, and miR-135a may have the potential to become key miRNA for tendon maturation and healing.

SUBMITTER: Omoto T

PROVIDER: S-EPMC9241168 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Downregulation of cholesterol biosynthesis genes in the forebrain of ERCC1-deficient mice.

Project description:Several genetic defects of the nucleotide excision repair (NER) pathway, including deficiency of the Excision Repair Cross-Complementing rodent repair deficiency, complementation group 1 (ERCC1), result in pre-mature aging, impaired growth, microcephaly and delayed development of the cerebellum. These phenotypes are recapitulated in Ercc1-knockout mice, which survive for up to 4 weeks after birth. Therefore, we analyzed cerebellar and hippocampal transcriptomes of these animals at 3 weeks of age to identify the candidate mechanisms underlying central nervous system abnormalities caused by inherited defects in NER. In the cerebellum, the most prominent change was the upregulation of genes associated with gliosis. Although Purkinje cell degeneration has been reported in some mouse strains with NER impairment, the transcripts whose downregulation is associated with Purkinje cell loss were mostly unaffected by the knockout of Ercc1. In the hippocampus, there was extensive downregulation of genes related to cholesterol biosynthesis. Reduced expression of these genes was also present in the neocortex of adult mice with reduced expression of ERCC1. These changes were accompanied by reduced mRNA expression of the transcription factor Sterol Regulatory Element Binding Transcription Factor-2 (SREBF2) which is a master regulator of cholesterol biosynthesis. The downregulation of forebrain cholesterol biosynthesis genes is a newly identified consequence of ERCC1 deficiency. Reduced cholesterol biosynthesis may contribute to the neurodevelopmental disruption that is associated with ERCC1 defects and several other NER deficiencies including Cockayne syndrome. In addition, this reduction may negatively affect the function of mature synapses.

| S-EPMC3345809 | biostudies-literature

Bmi1 Deficient Mice Exhibit Male Infertility.

Project description:Previous studies have demonstrated that the polycomb repressor Bmi1 is universally expressed in all types of testicular cells and might regulate the spermatogonia proliferation, however, it is unclear whether Bmi1 plays a critical role in maintaining normal male fertility in vivo. To answer this question, we first confirmed that Bmi1 is universally expressed in all types of testicular cells and found that the gene relative expression levels of Bmi1 in testis were the highest relative to other organs. Then we investigated the role of Bmi1 in maintaining normal male fertility using Bmi1 knockout male mouse model. Our results demonstrated that Bmi1 deficiency resulted in totally male infertility with smaller testis, severe oligospermia and sperm malformation. Mechanistically, decreased serum testosterone levels with down-regulating 3βHSD and 17βHSD expression levels, reduced germ cell proliferation, increased germ cell apoptosis with up-regulating p16, p19, p53 and p21 expression levels, increased reactive oxygen species (ROS) and H2O2 levels with down-regulating gene expression levels of anti-oxidant enzymes, and increased 8-OHdG and γ.H2AX positive cells in testis were observed in Bmi1 deficient mice compared with wild-type mice. These results indicate that Bmi1 deficiency results in male infertility by reducing testosterone syntheses, increasing oxidative stress and DNA damage, activating p16 and p19 signaling pathway, inhibiting germ cell proliferation and inducing germ cell apoptosis and sperm malformation. Thus, Bmi1 may be a novel and potential target for the clinic treatment of male infertility.

| S-EPMC5859480 | biostudies-literature

Calvarial bone development and suture closure in Dicer-deficient mice.

Project description:To evaluate whether lack of Dicer during calvaria development would lead to dysmorphology of calvaria and suture closure in mice.A conditional Dicer deficient under Osx promoter mouse was employed in this study. The 4- and 10-week-old conditional Dicer-deficient mice control littermates and Osx-cre transgenic mice were studied for calvarial bone morphology and suture closure. Dry skull, microcomputed tomography (?CT), histological and gene expression studies were investigated to evaluate the effect of Dicer deficiency on calvarial bone morphology and their related genes during calvaria development.The results elucidated that complete suture closure was observed in 10-week-old conditional Dicer-deficient mice while incomplete closure suture was observed in age-matched Osx-cre control mice. The ?CT and histological sections demonstrated complete fusion of posterior frontal suture and dysmorphic calvarial bones in Dicer deficient mice compared to the ones in their littermates and age-matched Osx-cre control mice. Gene expression study demonstrated significantly increased expression of suture and calvarial bone-related genes, that is Tgf-beta family, Bmp3, Msx2, Alx4, Runx2 and Osx in Dicer-deficient mice during suture closure time.The results suggest mature miRNAs are important for suture closure and calvarial morphology during calvaria development.

| S-EPMC5484058 | biostudies-other

TRAIL-deficient mice exhibit delayed regression of retinal neovascularization.

Project description:While it is well established that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various cell types, the role of TRAIL in regulation of retinal neovascularization (NV) has not been described. Here we determined the role of TRAIL in retinal NV during oxygen-induced retinopathy using TRAIL deficient ((-/-)) mice. TRAIL and its receptor, DR5, were expressed in wild-type retinas at all time points evaluated (postnatal days 12, 17, 21, 24) during oxygen-induced retinopathy and in age-matched room air control animals. Localization of TRAIL(+) cells within the neovascular tufts of hyperoxia- exposed wild-type mice suggested TRAIL plays a role in oxygen-induced retinopathy. Retinal vascular development appeared normal in the TRAIL(-/-) mice, except for a small but significant difference in the capillary-free zone surrounding major arteries. A minimal difference in avascularity was observed at postnatal day 12 in the retinas of TRAIL(-/-) mice after hyperoxia-exposure compared with wild-type mice, suggesting that TRAIL does not play a major role in the vaso-obliterative phase of oxygen-induced retinopathy. However, at the peak of NV, TRAIL(-/-) mice had a significant increase in retinal neovascularization. In addition, when NV naturally regresses in wild-type mice, TRAIL(-/-) mice continued to display significantly high levels of NV. This was attributed to a significant decrease in neovascular tuft cells undergoing apoptosis in TRAIL(-/-) mice. Together, these data strongly suggest that TRAIL plays a role in the control of retinal NV.

| S-EPMC2789602 | biostudies-literature

Cell-specific expression of artificial microRNAs targeting essential genes exhibit potent antitumor effect on hepatocellular carcinoma cells.

Project description:To achieve specific and potent antitumor effect of hepatocyte carcinoma cells, replication defective adenoviral vectors, namely rAd/AFP-amiRG, rAd/AFP-amiRE and rAd/AFP-amiRP, were constructed which were armed with artificial microRNAs (amiRs) targeting essential functional genes glyceraldehyde-3-phosphate dehydrogenase, eukaryotic translation initiation factor 4E and DNA polymerase α respectively under the control of a recombinant promoter comprised of human α-fetoprotein enhancer and basal promoter. The AFP enhancer/promoter showed specific high transcription activity in AFP-positive HCC cells Hep3B, HepG2 and SMMC7721, while low in AFP-negative cell Bcap37. All artificial microRNAs exhibited efficient knockdown of target genes. Decreased ATP production and protein synthesis was observed in rAd/AFP-amiRG and rAd/AFP-amiRE treated HCC cells. All three recombinant adenoviruses showed efficient blockage of cell cycle progression and significant suppression of HCC cells in vitro. In nude mice model bearing Hep3B xenograft, administration of rAd/AFP-amiRG showed potent antitumor effect. The strategy of tumor-specific knockdown of genes essential for cell survival and proliferation may suggest a novel promising approach for HCC gene therapy.

| S-EPMC4467396 | biostudies-literature

Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration.

Project description:The molecular mechanism underlying the selective vulnerability of certain neuronal populations associated with neurodegenerative diseases remains poorly understood. Basal autophagy is important for maintaining axonal homeostasis and preventing neurodegeneration. In this paper, we demonstrate that mice deficient in the metazoan-specific autophagy gene Epg5/epg-5 exhibit selective damage of cortical layer 5 pyramidal neurons and spinal cord motor neurons. Pathologically, Epg5 knockout mice suffered muscle denervation, myofiber atrophy, late-onset progressive hindquarter paralysis, and dramatically reduced survival, recapitulating key features of amyotrophic lateral sclerosis (ALS). Epg5 deficiency impaired autophagic flux by blocking the maturation of autophagosomes into degradative autolysosomes, leading to accumulation of p62 aggregates and ubiquitin-positive inclusions in neurons and glial cells. Epg5 knockdown also impaired endocytic trafficking. Our study establishes Epg5-deficient mice as a model for investigating the pathogenesis of ALS and indicates that dysfunction of the autophagic-endolysosomal system causes selective damage of neurons associated with neurodegenerative diseases.

| S-EPMC3601354 | biostudies-literature

Vav3-deficient mice exhibit a transient delay in cerebellar development.

Project description:Vav3 is a guanosine diphosphate/guanosine triphosphate exchange factor for Rho/Rac GTPases that has been involved in functions related to the hematopoietic system, bone formation, cardiovascular regulation, angiogenesis, and axon guidance. We report here that Vav3 is expressed at high levels in Purkinje and granule cells, suggesting additional roles for this protein in the cerebellum. Consistent with this hypothesis, we demonstrate using Vav3-deficient mice that this protein contributes to Purkinje cell dendritogenesis, the survival of granule cells of the internal granular layer, the timely migration of granule cells of the external granular layer, and to the formation of the cerebellar intercrural fissure. With the exception of the latter defect, the dysfunctions found in Vav3(-/-) mice only occur at well-defined postnatal developmental stages and disappear, or become ameliorated, in older animals. Vav2-deficient mice do not show any of those defects. Using primary neuronal cultures, we show that Vav3 is important for dendrite branching, but not for primary dendritogenesis, in Purkinje and granule cells. Vav3 function in the cerebellum is functionally relevant, because Vav3(-/-) mice show marked motor coordination and gaiting deficiencies in the postnatal period. These results indicate that Vav3 function contributes to the timely developmental progression of the cerebellum.

| S-EPMC2836963 | biostudies-literature

Astrocytic glutamate transporter 1 (GLT1) deficient mice exhibit repetitive behaviors.

Project description:Glutamatergic dysregulation is known to contribute to obsessive-compulsive disorder (OCD). Astrocytic glutamate transporter 1 (GLT1) is responsible for the majority of glutamate clearance. However, the role of GLT1 in OCD-like behavior remains unclear. Here, we found that astrocytic GLT1 deficient mice showed increased wheel running activity but reduced home cage activity. Notably, they exhibited elevated grooming/rearing time and increased repetitive behavior counts in contextual and cued fear conditioning. In addition, they showed increased rearing counts in the metabolic chamber, and also augmented rearing time and jumping counts in the open field test. Taken together, our findings suggest that astrocytic GLT1 deficiency promotes OCD-like repetitive behaviors.

| S-EPMC7572885 | biostudies-literature

<i>RAB11FIP5</i>-Deficient Mice Exhibit Cytokine-Related Transcriptomic Signatures.

Project description:Rab11 recycling endosomes are involved in immunological synaptic functions, but the roles of Rab11 family-interacting protein 5 (Rab11Fip5), one of the Rab11 effectors, in the immune system remain obscure. Our previous study demonstrated that RAB11FIP5 transcripts are significantly elevated in PBMCs from HIV-1-infected individuals, making broadly HIV-1-neutralizing Abs compared with those without broadly neutralizing Abs; however, the role of Rab11FiP5 in immune functions remains unclear. In this study, a RAB11FIP5 gene knockout (RAB11FIP5 -/-) mouse model was employed to study the role of Rab11Fip5 in immune responses. RAB11FIP5 -/- mice exhibited no perturbation in lymphoid tissue cell subsets, and Rab11Fip5 was not required for serum Ab induction following HIV-1 envelope immunization, Ab transcytosis to mucosal sites, or survival after influenza challenge. However, differences were observed in multiple transcripts, including cytokine genes, in lymphocyte subsets from envelope-immunized RAB11FIP5 -/- versus control mice. These included alterations in several genes in NK cells that mirrored observations in NKs from HIV-infected humans expressing less RAB11FIP5, although Rab11Fip5 was dispensable for NK cell cytolytic activity. Notably, immunized RAB11FIP5 -/- mice had lower IL4 expression in CD4+ T follicular helper cells and showed lower TNF expression in CD8+ T cells. Likewise, TNF-α production by human CD8+ T cells correlated with PBMC RAB11FIP5 expression. These observations in RAB11FIP5 -/- mice suggest a role for Rab11Fip5 in regulating cytokine responses.

| S-EPMC8050958 | biostudies-literature

Snm1-deficient mice exhibit accelerated tumorigenesis and susceptibility to infection.

Project description:The eukaryotic SNM1 gene family has been implicated in a number of cellular pathways, including repair of DNA interstrand cross-links, involvement in VDJ recombination, repair of DNA double-strand breaks, and participation in cell cycle checkpoint pathways. In particular, mammalian SNM1 has been shown to be required in a mitotic checkpoint that causes arrest of cells in prophase prior to chromosome condensation in response to spindle poisons. Here, we report on the phenotype of a knockout of Snm1 in the mouse. Snm1-/- mice are viable and fertile but exhibit a complex phenotype. Both homozygous and heterozygous mice show a decline in survival compared to wild-type littermates. In homozygous mutant males, this reduction in survival is principally due to bacterial infections in the preputial and mandibular glands and to a lesser extent to tumorigenesis, while in homozygous and heterozygous females, it is due almost solely to tumorigenesis. The high incidence of bacterial infections in the homozygous mutant males suggests an immune dysfunction; however, examinations of T- and B-cell development and immunoglobulin class switching did not reveal a defect in these pathways. Crossing of Snm1 mutant mice with a Trp53 null mutant resulted in an increase in mortality and a restriction of the tumor type to lymphomas, particularly those of the thymus. Taken together, these findings demonstrate that Snm1 is a tumor suppressor in mice that in addition has a role in immunity.

| S-EPMC1280277 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data