FAT10 knock out mice livers fail to develop Mallory–Denk bodies in the DDC mouse model

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is raising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behavior and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently lead to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about possible mechanism involved in OCD and ASD. Additionally, it shows that modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of high inherited risk of certain mental health conditions.

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FRI-281-IL-4 receptor alpha knock-out mice are protected against fibrotic NASH in a representative mouse model of non-alcoholic steatohepatitis

Journal of Hepatology ◽

10.1016/s0618-8278(19)31026-6 ◽

2019 ◽

Vol 70 (1) ◽

pp. e519

Author(s):

Muhammad Ashfaq-Khan ◽

Misbah Aslam ◽

Marcel Senkowski ◽

Detlef Schuppan

Keyword(s):

Mouse Model ◽

Knock Out ◽

Receptor Alpha ◽

Alcoholic Steatohepatitis ◽

Knock Out Mice

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RB depletion is required for the continuous growth of tumors initiated by loss of RB

PLoS Genetics ◽

10.1371/journal.pgen.1009941 ◽

2021 ◽

Vol 17 (12) ◽

pp. e1009941

Author(s):

Alex Doan ◽

Julia Arand ◽

Diana Gong ◽

Alexandros P. Drainas ◽

Yan Ting Shue ◽

...

Keyword(s):

Mouse Model ◽

Cancer Cells ◽

Mechanisms Of Action ◽

Thyroid Tumors ◽

Continuous Growth ◽

Knock Out ◽

Cycle Arrest ◽

Wide Range ◽

Knock Out Mice

The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation in vivo. In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to Rb knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function in vivo.

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A Pig-a conditional knock-out mice model mediated by Vav-iCre: stable GPI-deficient and mild hemolysis

Experimental Hematology and Oncology ◽

10.1186/s40164-022-00254-5 ◽

2022 ◽

Vol 11 (1) ◽

Author(s):

Yingying Chen ◽

Hui Liu ◽

Lijie Zeng ◽

Liyan Li ◽

Dan Lu ◽

...

Keyword(s):

Stem Cells ◽

Animal Model ◽

Mouse Model ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Basic Research ◽

Mice Model ◽

Hematopoietic Stem ◽

Knock Out ◽

Knock Out Mice

AbstractParoxysmal nocturnal hemoglobinuria is a clonal disease caused by PIG-A mutation of hematopoietic stem cells. At present, there is no suitable PNH animal model for basic research, therefore, it is urgent to establish a stable animal model. We constructed a Pig-a conditional knock-out mice model by ES targeting technique and Vav-iCre. The expressions of GPI and GPI-AP were almost completely absent in CKO homozygote mice, and the proportion of the deficiency remained stable from birth. In CKO heterozygote mice, the proportion of the deficiency of GPI and GPI-AP was partially absent and decreased gradually from birth until it reached a stable level at 3 months after birth and remained there for life. Compared with normal C57BL/6N mice and Flox mice, pancytopenia was found in CKO homozygous mice, and leukopenia and anemia were found in CKO heterozygotes mice. Meanwhile, in CKO mice, the serum LDH, TBIL, IBIL, complement C5b-9 levels were increased, and the concentration of plasma FHb was increased. Hemosiderin granulosa cells can be seen more easily in the spleens of CKO mice. What’s more, CKO mice had stable transcription characteristics. In conclusion, our mouse model has stable GPI-deficient and mild hemolysis, which may be an ideal in vivo experimental model for PNH.

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Dysregulation of DNA Methylation During Development as a Potential Mechanism Contributing to Obsessive Compulsive Disorders and Autism

Neurology and Neurobiology ◽

10.31487/j.nnb.2020.01.04 ◽

2020 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Catarina Cunha ◽

David Ashurov ◽

German Todorov ◽

Karthikeyan Mayilvahanan

Keyword(s):

Mouse Model ◽

Autism Spectrum ◽

Obsessive Compulsive ◽

Cancer Treatments ◽

Knock Out ◽

Compulsive Behaviour ◽

Treatment Priority ◽

Underlying Mechanisms ◽

Knock Out Mice ◽

Obsessive Compulsive Disorders

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is rising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behaviour and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently leads to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about the possible mechanisms involved in OCD and ASD. Additionally, it shows that the modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of the high inherited risk of certain mental health conditions.

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A New Mouse Model for Complete Congenital Stationary Night Blindness Due to Gpr179 Deficiency

International Journal of Molecular Sciences ◽

10.3390/ijms22094424 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4424

Author(s):

Elise Orhan ◽

Marion Neuillé ◽

Miguel de Sousa Dias ◽

Thomas Pugliese ◽

Christelle Michiels ◽

...

Keyword(s):

Mouse Model ◽

Night Blindness ◽

Signal Transmission ◽

Bipolar Cells ◽

Congenital Stationary Night Blindness ◽

Knock Out ◽

Intron 1 ◽

Knock Out Mice

Mutations in GPR179 lead to autosomal recessive complete congenital stationary night blindness (cCSNB). This condition represents a signal transmission defect from the photoreceptors to the ON-bipolar cells. To confirm the phenotype, better understand the pathogenic mechanism in vivo, and provide a model for therapeutic approaches, a Gpr179 knock-out mouse model was genetically and functionally characterized. We confirmed that the insertion of a neo/lac Z cassette in intron 1 of Gpr179 disrupts the same gene. Spectral domain optical coherence tomography reveals no obvious retinal structure abnormalities. Gpr179 knock-out mice exhibit a so-called no-b-wave (nob) phenotype with severely reduced b-wave amplitudes in the electroretinogram. Optomotor tests reveal decreased optomotor responses under scotopic conditions. Consistent with the genetic disruption of Gpr179, GPR179 is absent at the dendritic tips of ON-bipolar cells. While proteins of the same signal transmission cascade (GRM6, LRIT3, and TRPM1) are correctly localized, other proteins (RGS7, RGS11, and GNB5) known to regulate GRM6 are absent at the dendritic tips of ON-bipolar cells. These results add a new model of cCSNB, which is important to better understand the role of GPR179, its implication in patients with cCSNB, and its use for the development of therapies.

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