Role of Olfaction in the Conditioned Sucrose Preference of Sweet-Ageusic T1R3 Knockout Mice

Proto-oncogene tyrosine-protein kinase SRC (SRC), as other members of the SRC family kinases (SFK), plays an important role in regulating signal transduction by different cell surface receptors after changes in the cellular environment. Here, we reviewed the role of SRC in platelets and megakaryocytes (MK). In platelets, inactive closed SRC is coupled to the β subunit of integrin αIIbβ3 while upon fibrinogen binding during platelet activation, αIIbβ3-mediated outside-in signaling is initiated by activation of SRC. Active open SRC now further stimulates many downstream effectors via tyrosine phosphorylation of enzymes, adaptors, and especially cytoskeletal components. Functional platelet studies using SRC knockout mice or broad spectrum SFK inhibitors pointed out that SRC mediates their spreading on fibrinogen. On the other hand, an activating pathological SRC missense variant E527K in humans that causes bleeding inhibits collagen-induced platelet activation while stimulating platelet spreading. The role of SRC in megakaryopoiesis is much less studied. SRC knockout mice have a normal platelet count though studies with SFK inhibitors point out that SRC could interfere with MK polyploidization and proplatelet formation but these inhibitors are not specific. Patients with the SRC E527K variant have thrombocytopenia due to hyperactive SRC that inhibits proplatelet formation after increased spreading of MK on fibrinogen and enhanced formation of podosomes. Studies in humans have contributed significantly to our understanding of SRC signaling in platelets and MK.

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KH-type splicing regulatory protein is a new component of chromatoid body

Reproduction ◽

10.1530/rep-17-0169 ◽

2017 ◽

Vol 154 (6) ◽

pp. 723-733 ◽

Cited By ~ 1

Author(s):

Huijuan Zhang ◽

Guishuan Wang ◽

Lin Liu ◽

Xiaolin Liang ◽

Yu Lin ◽

...

Keyword(s):

Gene Expression ◽

Germ Cell ◽

Knockout Mice ◽

Binding Protein ◽

Regulatory Protein ◽

Somatic Cells ◽

Chromatoid Body ◽

Mechanistic Insight ◽

Insight Into

The chromatoid body (CB) is a specific cloud-like structure in the cytoplasm of haploid spermatids. Recent findings indicate that CB is identified as a male germ cell-specific RNA storage and processing center, but its function has remained elusive for decades. In somatic cells, KH-type splicing regulatory protein (KSRP) is involved in regulating gene expression and maturation of select microRNAs (miRNAs). However, the function of KSRP in spermatogenesis remains unclear. In this study, we showed that KSRP partly localizes in CB, as a component of CB. KSRP interacts with proteins (mouse VASA homolog (MVH), polyadenylate-binding protein 1 (PABP1) and polyadenylate-binding protein 2 (PABP2)), mRNAs (Tnp2 and Odf1) and microRNAs (microRNA-182) in mouse CB. Moreover, KSRP may regulate the integrity of CB via DDX5-miRNA-182 pathway. In addition, we found abnormal expressions of CB component in testes of Ksrp-knockout mice and of patients with hypospermatogenesis. Thus, our results provide mechanistic insight into the role of KSRP in spermatogenesis.

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Role of dopamine D1 receptors for κ-opioid–mediated locomotor activity and antinociception during the preweanling perioda study using D1 receptor knockout mice

Physiology & Behavior ◽

10.1016/s0031-9384(99)00223-1 ◽

2000 ◽

Vol 68 (4) ◽

pp. 585-590 ◽

Cited By ~ 6

Author(s):

P KARPER ◽

A NAZARIAN ◽

C CRAWFORD ◽

J DRAGO ◽

S MCDOUGALL

Keyword(s):

Locomotor Activity ◽

Knockout Mice ◽

D1 Receptor ◽

D1 Receptors ◽

Dopamine D1 Receptors

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Ameliorated course of glucose-6-phosphate isomerase (G6PI)-induced arthritis in IFN-γ receptor knockout mice exposes an arthritis-promoting role of IFN-γ

Journal of Autoimmunity ◽

10.1016/j.jaut.2010.12.006 ◽

2011 ◽

Vol 36 (2) ◽

pp. 161-169 ◽

Cited By ~ 11

Author(s):

Oliver Frey ◽

Tania Mitera ◽

Hilde Kelchtermans ◽

Evelien Schurgers ◽

Thomas Kamradt ◽

...

Keyword(s):

Knockout Mice ◽

Ifn Γ

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Regulation of the cognitive aging process by the transcriptional repressor RP58

10.1101/2021.09.18.460879 ◽

2021 ◽

Author(s):

Tomoko Tanaka ◽

Shinobu Hirai ◽

Hiroyuki Manabe ◽

Kentaro Endo ◽

Hiroko Shimbo ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Knockout Mice ◽

Cognitive Aging ◽

Critical Role ◽

Harmful Effect ◽

Transcriptional Repressor ◽

Repair Pathway ◽

Wild Type

Aging involves a decline in physiology which is a natural event in all living organisms. An accumulation of DNA damage contributes to the progression of aging. DNA is continually damaged by exogenous sources and endogenous sources. If the DNA repair pathway operates normally, DNA damage is not life threatening. However, impairments of the DNA repair pathway may result in an accumulation of DNA damage, which has a harmful effect on health and causes an onset of pathology. RP58, a zinc-finger transcriptional repressor, plays a critical role in cerebral cortex formation. Recently, it has been reported that the expression level of RP58 decreases in the aged human cortex. Furthermore, the role of RP58 in DNA damage is inferred by the involvement of DNMT3, which acts as a co-repressor for RP58, in DNA damage. Therefore, RP58 may play a crucial role in the DNA damage associated with aging. In the present study, we investigated the role of RP58 in aging. We used RP58 hetero-knockout and wild-type mice in adolescence, adulthood, or old age. We performed immunohistochemistry to determine whether microglia and DNA damage markers responded to the decline in RP58 levels. Furthermore, we performed an object location test to measure cognitive function, which decline with age. We found that the wild-type mice showed an increase in single-stranded DNA and gamma-H2AX foci. These results indicate an increase in DNA damage or dysfunction of DNA repair mechanisms in the hippocampus as age-related changes. Furthermore, we found that, with advancing age, both the wild-type and hetero-knockout mice showed an impairment of spatial memory for the object and increase in reactive microglia in the hippocampus. However, the RP58 hetero-knockout mice showed these symptoms earlier than the wild-type mice did. These results suggest that a decline in RP58 level may lead to the progression of aging.

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Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis

10.1101/2020.12.10.420695 ◽

2020 ◽

Author(s):

Benjamin Ng ◽

Anissa A. Widjaja ◽

Sivakumar Viswanathan ◽

Jinrui Dong ◽

Sonia P. Chothani ◽

...

Keyword(s):

Knockout Mice ◽

Lung Fibroblasts ◽

Loss Of Function ◽

Wild Type ◽

Reduced Body ◽

Body Weights ◽

Show Evidence ◽

Similarities And Differences ◽

The Impact

AbstractGenetic loss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and craniosynostosis. The impact of genetic LOF in IL11 has not been characterized. We generated IL11-knockout (Il11-/-) mice, which are born in normal Mendelian ratios, have normal hematological profiles and are protected from bleomycin-induced lung fibro-inflammation. Noticeably, baseline IL6 levels in the lungs of Il11-/- mice are lower than those of wild-type mice and are not induced by bleomycin damage, placing IL11 upstream of IL6. Lung fibroblasts from Il11-/- mice are resistant to pro-fibrotic stimulation and show evidence of reduced autocrine IL11 activity. Il11-/- female mice are infertile. Unlike Il11ra1-/- mice, Il11-/- mice do not have a craniosynostosis-like phenotype and exhibit mildly reduced body weights. These data highlight similarities and differences between LOF in IL11 or IL11RA while establishing further the role of IL11 signaling in fibrosis and stromal inflammation.

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Remyelination in experimentally demyelinated connexin 32 KnockOut mice

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2009000300020 ◽

2009 ◽

Vol 67 (2b) ◽

pp. 488-493

Author(s):

Adriano Tony Ramos ◽

Paulo César Maiorka ◽

Maria Lúcia Zaidan Dagli ◽

Fernando Yutaka Moniwa Hosomi ◽

Kalan Bastos Violin ◽

...

Keyword(s):

Knockout Mice ◽

Connexin 32 ◽

Ethidium Bromide Solution ◽

Normal Pattern ◽

Myelin Sheaths ◽

Transmission Electron ◽

Bromide Solution ◽

Sciatic Nerves ◽

Electron Microscopical

The aim of this study was to evaluate the role of connexin 32 (Cx 32) during remyelination of the peripheral nervous system, through a local injection of either 0,1% ethidium bromide solution or saline in the sciatic nerve of Cx 32 knockout mice. Euthanasia was performed ranging from 1, 2, 3, 7, 15, 21 to 30 days after injection. Histochemical, immunohistochemical, immunofluorescence and transmission electron microscopical techniques were used to analyze the development of the lesions. Within the sciatic nerves, Schwann cells initially showed signs of intoxication and rejected their sheaths; after seven days, some thin newly formed myelin sheaths with uneven compactness and redundant loops (tomacula) were conspicuous. We concluded that the regeneration of lost myelin sheaths within the PNS followed the pattern already reported for this model in other laboratory species. Therefore, these results suggest that absence of Cx 32 did not interfere with the normal pattern of remyelination in this model in young mice.

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Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice

Life ◽

10.3390/life11121325 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1325

Author(s):

Fenfen Li ◽

Xin Cui ◽

Jia Jing ◽

Shirong Wang ◽

Huidong Shi ◽

...

Keyword(s):

Dna Methylation ◽

Energy Expenditure ◽

Knockout Mice ◽

Dna Methyltransferase ◽

De Novo ◽

Brown Fat ◽

Chow Diet ◽

Female Mice ◽

Diet Induced Obesity

Obesity results from a chronic energy imbalance due to energy intake exceeding energy expenditure. Activation of brown fat thermogenesis has been shown to combat obesity. Epigenetic regulation, including DNA methylation, has emerged as a key regulator of brown fat thermogenic function. Here we aimed to study the role of Dnmt3b, a DNA methyltransferase involved in de novo DNA methylation, in the regulation of brown fat thermogenesis and obesity. We found that the specific deletion of Dnmt3b in brown fat promotes the thermogenic and mitochondrial program in brown fat, enhances energy expenditure, and decreases adiposity in female mice fed a regular chow diet. With a lean phenotype, the female knockout mice also exhibit increased insulin sensitivity. In addition, Dnmt3b deficiency in brown fat also prevents diet-induced obesity and insulin resistance in female mice. Interestingly, our RNA-seq analysis revealed an upregulation of the PI3K-Akt pathway in the brown fat of female Dnmt3b knockout mice. However, male Dnmt3b knockout mice have no change in their body weight, suggesting the existence of sexual dimorphism in the brown fat Dnmt3b knockout model. Our data demonstrate that Dnmt3b plays an important role in the regulation of brown fat function, energy metabolism and obesity in female mice.

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