scholarly journals The Spin1 interactor, Spindoc, is dispensable for meiotic division, but essential for haploid spermatid development in mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xue Jiang ◽  
Xiaoli Zhu ◽  
Yu Cheng ◽  
Muhammad Azhar ◽  
Xuemei Xing ◽  
...  
Keyword(s):  
Mouse Models ◽  
Meiotic Division ◽  
Knockout Mouse ◽  
Developmental Process ◽  
Physiological Role ◽  
Germline Development ◽  
Molecular Changes ◽  
Histone Marks ◽  
Downstream Signaling

AbstractIn mammals, germline development undergoes dramatic morphological and molecular changes and is epigenetically subject to intricate yet exquisite regulation. Which epigenetic players and how they participate in the germline developmental process are not fully characterized. Spin1 is a multifunctional epigenetic protein reader that has been shown to recognize H3 “K4me3-R8me2a” histone marks, and more recently the non-canonical bivalent H3 “K4me3-K9me3/2” marks as well. As a robust Spin1-interacting cofactor, Spindoc has been identified to enhance the binding of Spin1 to its substrate histone marks, thereby modulating the downstream signaling; However, the physiological role of Spindoc in germline development is unknown. We generated two Spindoc knockout mouse models through CRISPR/Cas9 strategy, which revealed that Spindoc is specifically required for haploid spermatid development, but not essential for meiotic divisions in spermatocytes. This study unveiled a new epigenetic player that participates in haploid germline development.

Understanding the physiological role of retinol-binding protein in vitamin A metabolism using transgenic and knockout mouse models

2003 ◽  
Vol 24 (6) ◽  
pp. 421-430 ◽  
Author(s):  
Loredana Quadro ◽  
Leora Hamberger ◽  
Vittorio Colantuoni ◽  
Max E. Gottesman ◽  
William S. Blaner
Keyword(s):  
Vitamin A ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Binding Protein ◽  
Physiological Role ◽  
Retinol Binding Protein ◽  
Vitamin A Metabolism

Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models

2003 ◽  
Vol 31 (1) ◽  
pp. 216-219 ◽  
Author(s):  
B. Viollet ◽  
F. Andreelli ◽  
S.B. Jørgensen ◽  
C. Perrin ◽  
D. Flamez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Glycogen Synthesis ◽  
Physiological Role ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To understand better the physiological role of the catalytic AMPK subunit isoforms, we generated two knockout mouse models with the α1 (AMPKα1−/−) and α2 (AMPKα2−/−) catalytic subunit genes deleted. No defect in glucose homoeostasis was observed in AMPKα1−/− mice. On the other hand, AMPKα2−/− mice presented high plasma glucose levels and low plasma insulin concentrations in the fed period and during the glucose tolerance test. Nevertheless, in isolated AMPKα2−/− pancreatic islets, glucose-stimulated insulin secretion was not affected. Surprisingly, AMPKα2−/− mice were insulin-resistant and had reduced muscle glycogen synthesis as assessed in vivo by the hyperinsulinaemic euglycaemic clamp procedure. Reduction of insulin sensitivity and glycogen synthesis were not dependent on the lack of AMPK in skeletal muscle, since mice expressing a dominant inhibitory mutant of AMPK in skeletal muscle were not affected and since insulin-stimulated glucose transport in incubated muscles in vitro was normal in AMPKα2−/− muscles. Furthermore, AMPKα2−/− mice have a higher sympathetic tone, as shown by increased catecholamine urinary excretion. Increased adrenergic tone could explain both decreased insulin secretion and insulin resistance observed in vivo in AMPKα2−/− mice. We suggest that the α2 catalytic subunit of AMPK plays a major role as a fuel sensor by modulating the activity of the autonomous nervous system in vivo.

scholarly journals Insights on the Functional Role of Beta-Glucans in Fungal Immunity Using Receptor-Deficient Mouse Models

2021 ◽  
Vol 22 (9) ◽  
pp. 4778
Author(s):  
Mark Joseph Maranan Desamero ◽  
Soo-Hyun Chung ◽  
Shigeru Kakuta
Keyword(s):  
Mouse Models ◽  
Deficient Mouse ◽  
Beta Glucan ◽  
Downstream Signaling ◽  
Beta Glucans ◽  
Fungal Immunity ◽  
Anti Fungal ◽  
Susceptibility And Resistance ◽  
Deficient Mice

Understanding the host anti-fungal immunity induced by beta-glucan has been one of the most challenging conundrums in the field of biomedical research. During the last couple of decades, insights on the role of beta-glucan in fungal disease progression, susceptibility, and resistance have been greatly augmented through the utility of various beta-glucan cognate receptor-deficient mouse models. Analysis of dectin-1 knockout mice has clarified the downstream signaling pathways and adaptive effector responses triggered by beta-glucan in anti-fungal immunity. On the other hand, assessment of CR3-deficient mice has elucidated the compelling action of beta-glucans in neutrophil-mediated fungal clearance, and the investigation of EphA2-deficient mice has highlighted its novel involvement in host sensing and defense to oral mucosal fungal infection. Based on these accounts, this review focuses on the recent discoveries made by these gene-targeted mice in beta-glucan research with particular emphasis on the multifaceted aspects of fungal immunity.

PHYSIOLOGICAL ROLE OF BRAIN ENDOTHELIN IN THE CENTRAL AUTONOMIC CONTROL: FROM NEURON TO KNOCKOUT MOUSE

1997 ◽  
Vol 51 (5) ◽  
pp. 545-579 ◽  
Author(s):  
TOMUYUKI KUWAKI ◽  
HIROKI KURIHARA ◽  
WEI HUA CAO ◽  
YUKIKO KURIHARA ◽  
MIYUKI UNEKAWA ◽  
...  
Keyword(s):  
Knockout Mouse ◽  
Physiological Role ◽  
Autonomic Control

scholarly journals ProMetIS, deep phenotyping of mouse models by combined proteomics and metabolomics analysis

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Alyssa Imbert ◽  
Magali Rompais ◽  
Mohammed Selloum ◽  
Florence Castelli ◽  
Emmanuelle Mouton-Barbosa ◽  
...  
Keyword(s):  
Mouse Models ◽  
Physiological Role ◽  
R Package ◽  
Level Data ◽  
Molecular Information ◽  
Number Of Individuals ◽  
Deep Phenotyping ◽  
Omics Data Integration

AbstractGenes are pleiotropic and getting a better knowledge of their function requires a comprehensive characterization of their mutants. Here, we generated multi-level data combining phenomic, proteomic and metabolomic acquisitions from plasma and liver tissues of two C57BL/6 N mouse models lacking the Lat (linker for activation of T cells) and the Mx2 (MX dynamin-like GTPase 2) genes, respectively. Our dataset consists of 9 assays (1 preclinical, 2 proteomics and 6 metabolomics) generated with a fully non-targeted and standardized approach. The data and processing code are publicly available in the ProMetIS R package to ensure accessibility, interoperability, and reusability. The dataset thus provides unique molecular information about the physiological role of the Lat and Mx2 genes. Furthermore, the protocols described herein can be easily extended to a larger number of individuals and tissues. Finally, this resource will be of great interest to develop new bioinformatic and biostatistic methods for multi-omics data integration.

Inhibiting Focal Adhesion Kinase Ameliorates Cyst Development in Polycystin-1–Deficient Polycystic Kidney Disease in Animal Model

2021 ◽  
Vol 32 (9) ◽  
pp. 2159-2174
Author(s):  
Jinzhao He ◽  
Shun Zhang ◽  
Zhiwei Qiu ◽  
Xiaowei Li ◽  
Huihui Huang ◽  
...  
Keyword(s):  
Mouse Models ◽  
Focal Adhesion ◽  
Knockout Mouse ◽  
Ex Vivo ◽  
Renal Cyst ◽  
Tubular Epithelial Cells ◽  
Polycystic Kidney ◽  
Content Type ◽  
Cyst Development

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is characterized by numerous cysts originating from renal tubules and is associated with significant tubular epithelial cell proliferation. Focal adhesion kinase (FAK) promotes tumor growth by regulating multiple proliferative pathways.MethodsWe established the forskolin (FSK)-induced three-dimensional (3D) Madin–Darby Canine Kidney cystogenesis model and 8-bromoadenosine-3`,5`-cyclic monophosphate–stimulated cyst formation in ex vivo embryonic kidney culture. Cultured human renal cyst–lining cells (OX-161) and normal tubular epithelial cells were treated with FAK inhibitors or transfected with green fluorescent protein–tagged FAK mutant plasmids for proliferation study. Furthermore, we examined the role of FAK in two transgenic ADPKD animal models, the kidney-specific Pkd1 knockout and the collecting duct–specific Pkd1 knockout mouse models.ResultsFAK activity was significantly elevated in OX-161 cells and in two ADPKD mouse models. Inhibiting FAK activity reduced cell proliferation in OX-161 cells and prevented cyst growth in ex vivo and 3D cyst models. In tissue-specific Pkd1 knockout mouse models, FAK inhibitors retarded cyst development and mitigated renal function decline. Mechanically, FSK stimulated FAK activation in tubular epithelial cells, which was blocked by a protein kinase A (PKA) inhibitor. Inhibition of FAK activation by inhibitors or transfected cells with mutant FAK constructs interrupted FSK-mediated Src activation and upregulation of ERK and mTOR pathways.ConclusionsOur study demonstrates the critical involvement of FAK in renal cyst development, suggests that FAK is a potential therapeutic target in treating patients with ADPKD, and highlights the role of FAK in cAMP-PKA–regulated proliferation.

scholarly journals Mouse models of altered protein kinase A signaling

2009 ◽  
Vol 16 (3) ◽  
pp. 773-793 ◽  
Author(s):  
Lawrence S Kirschner ◽  
Zhirong Yin ◽  
Georgette N Jones ◽  
Emilia Mahoney
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Mouse Models ◽  
Physiological Role ◽  
Gene Families ◽  
Current Data ◽  
Model Organisms ◽  
Signaling System ◽  
Kinase A

Protein kinase A (PKA) is an evolutionarily conserved protein which has been studied in model organisms from yeast to man. Although the cAMP–PKA signaling system was the first mammalian second messenger system to be characterized, many aspects of this pathway are still not well understood. Owing to findings over the past decade implicating PKA signaling in endocrine (and other) tumorigenesis, there has been renewed interest in understanding the role of this pathway in physiology, particularly as it pertains to the endocrine system. Because of the availability of genetic tools, mouse modeling has become the pre-eminent system for studying the physiological role of specific genes and gene families as a means to understanding their relationship to human diseases. In this review, we will summarize the current data regarding mouse models that have targeted the PKA signaling system. These data have led to a better understanding of both the complexity and the subtlety of PKA signaling, and point the way for future studies, which may help to modulate this pathway for therapeutic effect.

scholarly journals 094 Characterisation of Novel Knockout Mouse Models to Investigate the Role of B55α in the Heart

2020 ◽  
Vol 29 ◽  
pp. S79
Author(s):  
N. Sergienko ◽  
D. Donner ◽  
H. Kiriazis ◽  
J. McMullen ◽  
K. Weeks
Keyword(s):  
Mouse Models ◽  
Knockout Mouse
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