Brain transcriptome study through CRISPR/Cas9 mediated mouse Dip2c gene knock-out

Oo, Zin Mar; Adlat, Salah; Sah, Rajiv Kumar; Myint, May Zun Zaw; Hayel, Farooq; Chen, Yang; Htoo, Hsu; Bah, Fatoumata Binta; Chan, Mi Kaythi; Zhang, Luqing; Feng, Xuechao; Zheng, Yaowu

doi:10.1016/j.gene.2020.144975

Cited by 22 publications

(24 citation statements)

References 23 publications

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“…Whereas zebrafish clusters had limited expression of ephrin receptors and their ligands ( epha4a , efnb3a , efnb3b , and ephb2b ) or semaphorins ( sema3b and sema3fa ), mouse clusters showed robust expression of Epha4 , Efnb3 , Ephb2 , Sema3f , and Sema6a , with some cluster bias. In addition, several other well-known facilitators of axon outgrowth, fasciculation and synaptogenesis were expressed in both species ( dip2ca / Dip2c, dscama / Dscam, l1cam1a / L1cam , and ncam1b / Ncam1 ) ( Purohit et al, 2012 ; Montesinos, 2014 ; Oo et al, 2020 ). The ZF1-3 clusters had higher expression of dscamb whereas the ZF4 cluster primarily expressed dscaml1 ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

Single Cell Transcriptomic Analysis of Spinal Dmrt3 Neurons in Zebrafish and Mouse Identifies Distinct Subtypes and Reveal Novel Subpopulations Within the dI6 Domain

González

Jakobsson

Vieillard

et al. 2021

Front. Cell. Neurosci.

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The spinal locomotor network is frequently used for studies into how neuronal circuits are formed and how cellular activity shape behavioral patterns. A population of dI6 interneurons, marked by the Doublesex and mab-3 related transcription factor 3 (Dmrt3), has been shown to participate in the coordination of locomotion and gaits in horses, mice and zebrafish. Analyses of Dmrt3 neurons based on morphology, functionality and the expression of transcription factors have identified different subtypes. Here we analyzed the transcriptomes of individual cells belonging to the Dmrt3 lineage from zebrafish and mice to unravel the molecular code that underlies their subfunctionalization. Indeed, clustering of Dmrt3 neurons based on their gene expression verified known subtypes and revealed novel populations expressing unique markers. Differences in birth order, differential expression of axon guidance genes, neurotransmitters, and their receptors, as well as genes affecting electrophysiological properties, were identified as factors likely underlying diversity. In addition, the comparison between fish and mice populations offers insights into the evolutionary driven subspecialization concomitant with the emergence of limbed locomotion.

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Section: Resultsmentioning

confidence: 99%

Single Cell Transcriptomic Analysis of Spinal Dmrt3 Neurons in Zebrafish and Mouse Identifies Distinct Subtypes and Reveal Novel Subpopulations Within the dI6 Domain

González

Jakobsson

Vieillard

et al. 2021

Front. Cell. Neurosci.

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“…In addition, the DIP2C gene is located on the minimal region of the overlap of the deletions (24). It is highly expressed in the brain and encompasses various neurological functions, such as "memory, " "neuropeptide signaling pathway, " and "response to amphetamine" according to a gene ontology analysis in the DIP2C gene knock-out mice (12). The deletion of DIP2C could induce the cell enlargement and growth retardation by stimulating DNA methylation (27).…”

Section: Discussionmentioning

confidence: 99%

“…The DIP2C gene encodes a member of the disco-interacting protein homolog two family with two other isoforms, DIP2A and DIP2B. It is a candidate for developmental dyslexia and autism (12). The LARP4B gene encodes a member of an evolutionarily conserved protein family implicated in RNA metabolism and translation (13).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Clinical Description of a Patient Carrying a 12.48 Mb Microdeletion Involving the 10p13–15.3 Region

Pan

2021

Front. Pediatr.

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Partial deletion of 10p chromosome is a rare chromosomal aberration. Submicroscopic deletion of 10p15.3 is mainly related to cognitive deficits, speech disorders, motor delay, and hypotonia with the deleted region ranging from 0.15 to 4 Mb. The clinical phenotype is mainly determined by the ZMYND11 and DIP2C genes. Here, we report a rare case of feeding difficulties, hypocalcemia, and psychomotor retardation. Our patient has a 12.48 Mb deletion in 10p15.3–10p13, which is the second case of large 10p deletion among reported cases thus far.

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“…Cas 9 plasmid (CAS9P-1EA; Sigma-Aldrich; Merck KGaA) and sgRNA were microinjected into the fertilized eggs of C57BL/6 mice (female, 12 mice, obtained from Shanghai Experimental Animal Center and housed in the Animal Center of The First Affiliated Hospital of Kangda College of Nanjing Medical University at 23–25°C with a relative humidity of 50–70%, 12-h light/dark cycle and free food/water access). Fertilized eggs were transplanted into the uterus of C57BL/6 mice to obtain positive F0 mice, which were confirmed by PCR with the methods mentioned in the reverse transcription-quantitative (RT-q) PCR subsection and sequencing ( 19 ) (data not shown). A stable F1 generation mouse model was obtained by mating positive F0 generation mice with C57BL/6 mice and used in experiment II to generate the LPS+AKR1C1 −/− group.…”

Section: Methodsmentioning

confidence: 97%

AKR1C1 alleviates LPS‑induced ALI in mice by activating the JAK2/STAT3 signaling pathway

Wang

Yang

et al. 2021

Mol Med Rep

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Acute lung injury (ALI) is a respiratory tract disease characterized by increased alveolar/capillary permeability, lung inflammation and structural damage to lung tissues, which can progress and transform into acute respiratory distress syndrome (ARDS). Although there are several treatment strategies available to manage this condition, there is still no specific cure for ALI. Aldo-keto reductase family 1 member C1 (AKR1C1) is a member of the aldo-keto reductase superfamily, and is a well-known Nrf2 target gene and an oxidative stress gene. The aim of the present study was to investigate the effects of AKR1C1 on a lipopolysaccharide (LPS)-induced ALI model. After mice received LPS treatment, the mRNA expression levels of AKR1C1 in the bronchoalveolar lavage fluid and serum were measured using reverse transcription-quantitative PCR and its relationship with the inflammatory factors and malondialdehyde levels were determined using correlation analysis. Next, AKR1C1 was overexpressed or knocked out in mice, and subsequently ALI was induced in mice using LPS. The severity of ALI, oxidative stress and inflammation in the lungs were measured, and the potential involvement of the Janus kinase 2 (JAK2)/signal transduction activator of transcription 3 (STAT3) signaling pathway was assessed by measuring the changes of lung injury parameters after the agonists of JAK2/STAT3 pathway, including interleukin (IL)-6 and colivelin, were administrated to mice. The results revealed that AKR1C1 expression was decreased in the LPS-induced ALI mouse model. AKR1C1 expression was inversely correlated with serum tumor necrosis factor-α, IL-6 and malondialdehyde levels, and positively correlated with serum IL-10 levels. AKR1C1 overexpression significantly attenuated lung injury, as shown by the changes in Evans blue leakage in the lung, lung wet/dry weight ratio, PaO 2 /FIO 2 ratio, survival rate of mice and histological lung changes. In addition, the JAK2/STAT3 signaling pathway was significantly deactivated by AKR1C1 +/+ . When AKR1C1 +/+ mice were treated with JAK2/STAT3 agonists, the effects of AKR1C1 overexpression on lung injury and oxidative stress were abolished. In conclusion, AKR1C1 may protect against oxidative stress and serve as a negative regulator of inflammation in ALI/ARDS. In addition, the JAK2/STAT3 signaling pathway could participate in the protective effects of AKR1C1 against ALI.

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Brain transcriptome study through CRISPR/Cas9 mediated mouse Dip2c gene knock-out

Cited by 22 publications

References 23 publications

Single Cell Transcriptomic Analysis of Spinal Dmrt3 Neurons in Zebrafish and Mouse Identifies Distinct Subtypes and Reveal Novel Subpopulations Within the dI6 Domain

Single Cell Transcriptomic Analysis of Spinal Dmrt3 Neurons in Zebrafish and Mouse Identifies Distinct Subtypes and Reveal Novel Subpopulations Within the dI6 Domain

Case Report: Clinical Description of a Patient Carrying a 12.48 Mb Microdeletion Involving the 10p13–15.3 Region

AKR1C1 alleviates LPS‑induced ALI in mice by activating the JAK2/STAT3 signaling pathway

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