scholarly journals Defect of LSS Disrupts Lens Development in Cataractogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Minglei Zhao ◽  
Tingfang Mei ◽  
Bizhi Shang ◽  
Bin Zou ◽  
Qing Lian ◽  
...  
Keyword(s):  
Mouse Model ◽  
Congenital Cataract ◽  
Eye Lens ◽  
Rna Seq ◽  
Lens Development ◽  
Critical Determinant ◽  
Congenital Cataracts ◽  
Delayed Differentiation ◽  
Neonatal Lethality ◽  
Fiber Organization

Congenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of various cataract-causing mutant crystallins; however, its roles in lens development remain largely unknown. In our study, we generated a mouse model harboring Lss G589S mutation, which is homologous to cataract-causing G588S mutation in human LSS. LssG589S/G589S mice exhibited neonatal lethality at postal day 0 (P0), whereas these mice showed severe opacity in eye lens. Also, we found that cataract was formed at E17.5 after we examined the opacity of embryonic lens from E13.5 to E18.5. Moreover, disrupted lens differentiation occurred at E14.5 prior to formation of the opacity of eye lens, shown as delayed differentiation of lens secondary fiber and disordered lens fiber organization. In addition, RNA-seq analysis indicated that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our findings provide clear evidence that a mouse model harboring a homozygous Lss G589S mutation can recapitulate human congenital cataract. Our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understanding LSS defects in cataractogenesis and developing therapies for cataracts.

scholarly journals Maternal factor PABPN1L is essential for maternal mRNA degradation during maternal-to-zygotic transition

2020 ◽  
Author(s):  
Ying Wang ◽  
Tianhao Feng ◽  
Xiaodan Shi ◽  
Siyu Liu ◽  
Zerui Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Large Scale ◽  
Mrna Degradation ◽  
Female Infertility ◽  
Control Group ◽  
Rna Seq ◽  
Cell Stage ◽  
Maternal Mrna ◽  
Maternal To Zygotic Transition ◽  
Group A

AbstractInfertility affects 10% - 15% of families worldwide. However, the pathogenesis of female infertility caused by abnormal early embryonic development is not clear. We constructed a mouse model (Pabpn1l -/-) simulating the splicing abnormality of human PABPN1L and found that the female was sterile and the male was fertile. The Pabpn1l -/- oocytes can be produced, ovulated and fertilized normally, but cannot develop beyond the 2-cell stage. Using RNA-Seq, we found a large-scale upregulation of RNA in Pabpn1l -/- MII oocytes. Of the 2401 transcripts upregulated in Pabpn1l-/- MII oocytes, 1523 transcripts (63.4%) were also upregulated in Btg4 -/- MII oocytes, while only 53 transcripts (2.2%) were upregulated in Ythdf2 -/- MII oocytes. We documented that transcripts in zygotes derived from Pabpn1l -/- oocytes have a longer poly(A) tail than the control group, a phenomenon similar to that in Btg4-/- mice. Surprisingly, the poly(A) tail of these mRNAs was significantly shorter in the Pabpn1l -/- MII oocytes than in the Pabpn1l +/+. These results suggest that PABPN1L is involved in BTG4-mediated maternal mRNA degradation, and may antagonize poly(A) tail shortening in oocytes independently of its involvement in maternal mRNA degradation. Thus, PABPN1L variants could be a genetic marker of female infertility.

scholarly journals Changes in the Fluorescence Tracking of NaV1.6 Protein Expression in a BTBR T+Itpr3tf/J Autistic Mouse Model

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Musaad A. Alshammari ◽  
Mohammad R. Khan ◽  
Fawaz Alasmari ◽  
Abdulaziz O. Alshehri ◽  
Rizwan Ali ◽  
...  
Keyword(s):  
Mouse Model ◽  
Western Blot ◽  
Neuronal Excitability ◽  
Autism Spectrum ◽  
Wild Type ◽  
Western Blot Assay ◽  
Critical Determinant ◽  
Molecular Features ◽  
Voltage Gated Sodium Channels ◽  
Wild Type Control

The axon initial segment (AIS), the site of action potential initiation in neurons, is a critical determinant of neuronal excitability. Growing evidence indicates that appropriate recruitment of the AIS macrocomplex is essential for synchronized firing. However, disruption of the AIS structure is linked to the etiology of multiple disorders, including autism spectrum disorder (ASD), a condition characterized by deficits in social communication, stereotyped behaviors, and very limited interests. To date, a complete understanding of the molecular components that underlie the AIS in ASD has remained elusive. In this research, we examined the AIS structure in a BTBR T+Itpr3tf/J mouse model (BTBR), a valid model that exhibits behavioral, electrical, and molecular features of autism, and compared this to the C57BL/6J wild-type control mouse. Using Western blot studies and high-resolution confocal microscopy in the prefrontal frontal cortex (PFC), our data indicate disrupted expression of different isoforms of the voltage-gated sodium channels (NaV) at the AIS, whereas other components of AIS such as ankyrin-G and fibroblast growth factor 14 (FGF14) and contactin-associated protein 1 (Caspr) in BTBR were comparable to those in wild-type control mice. A Western blot assay showed that BTBR mice exhibited a marked increase in different sodium channel isoforms in the PFC compared to wild-type mice. Our results provide potential evidence for previously undescribed mechanisms that may play a role in the pathogenesis of autistic-like phenotypes in BTBR mice.

scholarly journals RNA-Seq Analysis of Spinal Cord Tissues from hPFN1G118V Transgenic Mouse Model of ALS at Pre-symptomatic and End-Stages of Disease

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Caroline Barham ◽  
Daniel Fil ◽  
Stephanie D. Byrum ◽  
Yasir Rahmatallah ◽  
Galina Glazko ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Rna Seq

scholarly journals Brain RNA-Seq Profiling of the Mucopolysaccharidosis Type II Mouse Model

2017 ◽  
Vol 18 (5) ◽  
pp. 1072 ◽  
Author(s):  
Marika Salvalaio ◽  
Francesca D’Avanzo ◽  
Laura Rigon ◽  
Alessandra Zanetti ◽  
Michela D’Angelo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Rna Seq ◽  
Mucopolysaccharidosis Type Ii

scholarly journals Comparative RNA-Seq Transcriptome Analysis on Pulmonary Inflammation in a Mouse Model of Asthma–COPD Overlap Syndrome

2021 ◽  
Vol 9 ◽  
Author(s):  
Pei Ma ◽  
Shuyi Li ◽  
Hui Yang ◽  
Jiqiao Yuan ◽  
Ziqian Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Molecular Mechanisms ◽  
Pulmonary Inflammation ◽  
Clinical Syndrome ◽  
Overlap Syndrome ◽  
Mouse Lung ◽  
Control Group ◽  
Chronic Obstructive ◽  
Rna Seq ◽  
Immune System Activation

Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a severe clinical syndrome characterized to describe patients with both asthma and COPD clinical characteristics, which has posed a serious threat to patients’ quality of life and life safety. However, there are many difficulties and uncertainties in its diagnosis and treatment in clinic; especially, its animal model has not been fully and thoroughly established, and the evaluation of therapeutic drugs is still in its infancy. Here, we used ovalbumin (OVA), lipopolysaccharide (LPS), and smoke costimulation to establish an ACO mouse model and then used RNA-seq technology to detect gene expression in mouse lung tissue. The results showed that ACO mice showed an overlap syndrome of asthma and COPD in lung histological changes and the levels of inflammatory cytokines in bronchoalveolar lavage fluid. The RNA-seq analysis results showed that 6,324 differentially expressed genes (DEGs) were screened between the ACO group and the control group, of which 2,717 (42.7%) were downregulated, and 3,607 (57.3%) were upregulated. Metascape analysis results showed that in the ACO model we established, due to the damage of the respiratory system, the accumulated diseased tissue involves lung, spleen, blood, bone marrow, thymus, etc. It has certain characteristics of pneumonia, pulmonary fibrosis, and chronic obstructive airway disease, lung tumors, rheumatoid arthritis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were enriched in inflammation, immune system activation and imbalance, cell proliferation, and adhesion migration, and the upstream signaling pathways of inflammation were mainly affected by HLA-DRA, SYK, CTLA4, VAV1, NRAS, and JAK3. In short, our research established a mouse model that can better simulate the clinicopathological characteristics of ACO and suggested the foundations in elucidating the molecular mechanisms for pulmonary inflammation and fibrosis in ACO. This work may help further research and contribute substantially to prevention and clinical treatment of ACO in the future.

scholarly journals RNA Sequencing Reveals Novel LncRNAs/mRNAs Network Associated with Puerarin-mediated Inhibition of Cardiac Hypertrophy in Mice

2021 ◽  
Author(s):  
Shan Ye ◽  
Wei-Yang Chen ◽  
Caiwen Ou ◽  
Min-Sheng Chen
Keyword(s):  
Mouse Model ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Rna Sequencing ◽  
Expression Patterns ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Biological Processes ◽  
Rna Seq ◽  
Qrt Pcr

Abstract Background: Evidence has demonstrated that puerarin is a potential drug for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs in a cardiac hypertrophy mouse model after puerarin treatment.Methods: A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to systematically analyze global gene expression. The target lncRNAs were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression (CNC) network was established to find the interaction of lncRNAs and mRNAs. The molecular functions, biological processes, molecular components and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyto Encyclopedia of Genes and Genomes (KEGG) pathways analysis.Results: Puerarin exhibited obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC upregulated 19 lncRNAs and downregulated 18 lncRNAs, which could be revised by puerarin treatment (Fold change ≥ 3 and P< 0.05). Expression alterations of selected lncRNAs ENSMUST00000125726, ENSMUST00000143044 and ENSMUST00000212795 were confirmed by qRT-PCR. Pearson’s correlation coefficients of co-expression levels suggested that there was interactive relationship between those 3 validated altered lncRNAs and 5,500 mRNAs (r > 0.95 or r < −0.95). Those co-expressed mRNAs were enriched in some important biological processes such as vesicle-mediated transport, sin 3 complex, and translation initiation factor activity. KEGG analyses suggested that those lncRNA-interacted mRNAs were enriched in RNA transport, ribosome biogenesis in eukaryotes and proteasome signaling pathway. Conclusion: Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the ENSMUST00000125726 /ENSMUST00000143044 / ENSMUST00000212795 -mRNAs network.

scholarly journals MO034ANALYSIS OF A MOUSE MODEL FOR MCTO DUE TO THE MUTATION OF MAFB TRANSACTIVATION DOMAIN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Toshiaki Usui ◽  
Naoki Morito ◽  
Yuki Tsunakawa ◽  
Hyojung JEON ◽  
Michito Hamada ◽  
...  
Keyword(s):  
Body Weight ◽  
Mouse Model ◽  
Histological Analysis ◽  
Sequencing Analysis ◽  
Transactivation Domain ◽  
Lower Body ◽  
Rna Seq ◽  
Isolated Glomeruli ◽  
Lower Body Weight ◽  
Tarsal Bones

Abstract Background and Aims Transcription factor MafB in podocytes is essential for podocyte differentiation and maintenance. Previous works identified a missense mutation in the transactivation domain of MAFB as the cause of multicentric carpotarsal osteolysis (MCTO). MCTO is a condition involving progressive osteolysis of the carpal and tarsal bones. MCTO patients also develop with focal segmental glomerulosclerosis (FSGS) and renal failure (MCTO nephropathy). However, the pathogenesis of MCTO in vivo is unclear. Method In order to address this question, we generated an MCTO mouse model using the CRISPR/Cas9-mediated genome editing. This mouse has a human MCTO mutation c.176C&gt;T, (p.Pro59Leu). Mafb MCTO/ MCTO mice were obtained by crossing Mafb MCTO/WT mice. Control animals were Mafb WT/WT mice. Sequencing analysis was performed to confirm the integration of the MCTO mutation on F2 generations. We checked urine of these mice every 4 weeks, and biochemical and histological analysis were performed at 26 weeks-ages. RNA-seq analysis of the isolated glomeruli of these mice was performed at 10 weeks-ages. Results Interestingly, MafbMCTO/MCTO newborn mice exhibited a 10% lower body weight than control mice. The differences were still observed at 2 weeks, with Mafb MCTO/MCTO mice presenting a 23% lower body weight than control animals. The length of femoral bones in Mafb MCTO/MCTO mice was shorter than that of control. MCTO model mice exhibit growth deficiency. In addition, Mafb MCTO/ MCTO mice resulted in albuminuria at 4 weeks-ages from postnatal periods and became persistent. Renal histological analysis in adult stage revealed FSGS-like glomerular lesions in Mafb MCTO/ MCTO mice. In electron microscope analysis, microvillous transformation of the foot processes of podocytes in Bowman’s space and foot processes effacements were seen in Mafb MCTO/ MCTO mice. These phenotypes are similar to that seen in MCTO nephropathy patients. Subsequently, we performed RNA-seq analysis of isolated glomeruli to gain insight into the molecular mechanism of the MCTO mutation. We found Cldn1, gene expression in mature podocytes caused profound proteinuria, was significantly increased in Mafb MCTO/ MCTO glomeruli. Conclusion This study is significant for revealing the mechanism of MCTO and contributes to the development of an alternative treatment against MCTO nephropathy by providing model mice for use.

A reinvestigation of some of the tissue movements involved in the formation of the neural tube and the eye/lens system of Triturus alpestris and Xenopus laevis

Development ◽  
1966 ◽  
Vol 16 (3) ◽  
pp. 431-438
Author(s):  
R. S. Lowery
Keyword(s):  
Xenopus Laevis ◽  
Neural Tube ◽  
Subsequent Development ◽  
Neural Plate ◽  
Eye Lens ◽  
Optic Vesicle ◽  
Lens System ◽  
Lens Development ◽  
Triturus Alpestris ◽  
Optic Cup

Since the beginning of the century the generally accepted scheme of eye/lens development has been that proposed by Spemann (1901) and later confirmed by numerous workers. According to this scheme the two presumptive components of the definitive eye, the optic cup and the lens, are spatially separated at the flat neural plate stage. They later come into apposition as a result of tissue movements which occur during the formation of the neural tube; the optic vesicle then provides an inductive stimulus for the subsequent development of the presumptive lens tissue. Spemann's suggestions concerning the tissue movements involved in the early formation of the eye/lens system do not appear to have been fundamentally questioned until the publication of a number of papers by Chanturishvili (1943, 1949,1958,1959,1962), although the theory of lens induction has been modified by workers such as Liedke (1955), Jacobson (1963) and von Woellwarth (1962).

Our experience in the surgical treatment of congenital cataract

Reflection ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25-27
Author(s):  
I. V. Kuznetsov ◽  
◽  
N. V. Pasikova ◽  
Keyword(s):  
Surgical Treatment ◽  
General Anesthesia ◽  
Congenital Cataract ◽  
Functional Results ◽  
Clinical Analysis ◽  
Early Postoperative Period ◽  
Congenital Cataracts ◽  
Initial Appointment ◽  
Examination Methods ◽  
Preoperative Examination

Aim. To present our experience and evaluate the results of surgical treatment of congenital cataracts. Methods. A clinical analysis of the results of congenital cataract aspiration in 16 children (22 eyes) aged 2 months to 5 years is performed. Bilateral cataract was determined in 6 children, unilateral – in 10. Preoperative examination of children aged 3–5 years was carried out in a standard way. Children younger than 3 years of age at the initial appointment underwent non-contact examination methods, the remaining studies were performed under general anesthesia in the operating room immediately before surgery. Congenital cataract phacoaspiration was performed under general anesthesia using the Stellaris microsurgical system (Bausch and Lomb, USA) through a 1.2-mm paracentesis in the lens irrigation-aspiration regime. Hydrophobic IOL models were implanted. The posterior lens capsule was preserved in all cases. Mandatory was the appointment of cycloplegics in drops in the early postoperative period. Results. An increase in visual acuity (from 0.03 to 0.7) occurred in all cases. However, presence of obscuration amblyopia of varying degrees required regular courses of pleoptic treatment. Conclusions. The effectiveness of congenital cataracts phacoaspiration is ensured by the fulfillment of federal clinical recommendations, however, sutureless surgery allows achieving high functional results in the treatment of this pathology. Key words: congenital cataract; phacoaspiration; intraocular lens.

Sign in / Sign up

Export Citation Format

Share Document