scholarly journals Easi-CRISPR for creating knock-in and conditional knockout mouse models using long ssDNA donors

2017 ◽  
Vol 13 (1) ◽  
pp. 195-215 ◽  
Author(s):  
Hiromi Miura ◽  
Rolen M Quadros ◽  
Channabasavaiah B Gurumurthy ◽  
Masato Ohtsuka
Keyword(s):  
Mouse Models ◽  
Knockout Mouse ◽  
Conditional Knockout ◽  
Conditional Knockout Mouse

scholarly journals Does murine spermatogenesis require WNT signalling? A lesson from Gpr177 conditional knockout mouse models

2016 ◽  
Vol 7 (6) ◽  
pp. e2281-e2281 ◽  
Author(s):  
Su-Ren Chen ◽  
J-X Tang ◽  
J-M Cheng ◽  
X-X Hao ◽  
Y-Q Wang ◽  
...  
Keyword(s):  
Mouse Models ◽  
Knockout Mouse ◽  
Wnt Signalling ◽  
Conditional Knockout ◽  
Conditional Knockout Mouse

Central nervous system pathology in MFP2 deficiency: Insights from general and conditional knockout mouse models

Biochimie ◽  
2014 ◽  
Vol 98 ◽  
pp. 119-126 ◽  
Author(s):  
Simon Verheijden ◽  
Lien Beckers ◽  
Stephanie De Munter ◽  
Paul P. Van Veldhoven ◽  
Myriam Baes
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Conditional Knockout ◽  
Central Nervous System Pathology ◽  
Conditional Knockout Mouse

scholarly journals Irradiation of Nf1 mutant mouse models of spinal plexiform neurofibromas drives pathologic progression and decreases survival

2021 ◽  
Author(s):  
Danny Laurent ◽  
Abbi E Smith ◽  
Waylan K Bessler ◽  
Marc Mendonca ◽  
Helen Chin-Sinex ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mouse Models ◽  
Conditional Knockout ◽  
Benign Neoplasms ◽  
Neoplastic Progression ◽  
Plexiform Neurofibromas ◽  
Normal Tissues ◽  
Peripheral Nerve Sheath Tumors ◽  
Conditional Knockout Mouse ◽  
Therapeutic Irradiation

Abstract Background Genetically susceptible individuals can develop malignancies after irradiation of normal tissues. In the context of therapeutic irradiation, it is not known whether irradiating benign neoplasms in susceptible individuals promotes neoplastic transformation and worse clinical outcomes. Individuals with Neurofibromatosis 1 (NF1) are susceptible to both radiation-induced second malignancies and spontaneous progression of plexiform neurofibromas (PNs) to malignant peripheral nerve sheath tumors (MPNSTs). The role of radiotherapy in the treatment of benign neoplasms such as PNs is unclear. Methods To test whether radiotherapy promotes neoplastic progression of PNs and reduces overall survival, we administered spinal irradiation (SI) to conditional knockout mouse models of NF1-associated PNs in two germline contexts: Nf1 fllfl; PostnCre + and Nf1 fl/-; PostnCre +. Both genotypes develop extensive Nf1 null spinal PNs, modeling PNs in NF1 patients. A total of 101 mice were randomized to 0 Gy, 15 Gy (3 Gy x 5), or 30 Gy (3 Gy x 10) of spine-focused, fractionated SI and aged until signs of illness. Results SI decreased survival in both Nf1 fllfl mice and Nf1 fl/- mice, with the worst overall survival occurring in Nf1 fl/- mice receiving 30 Gy. SI was also associated with increasing worrisome histologic features along the PN-MPNST continuum in PNs irradiated to higher radiation doses. Conclusions This pre-clinical study provides experimental evidence that irradiation of pre-existing PNs reduces survival and may shift PNs to higher grade neoplasms.

scholarly journals A Conditional Knockout Mouse Model Reveals That Calponin-3 Is Dispensable for Early B Cell Development

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0128385 ◽  
Author(s):  
Alexandra Flemming ◽  
Qi-Quan Huang ◽  
Jian-Ping Jin ◽  
Hassan Jumaa ◽  
Sebastian Herzog
Keyword(s):  
Mouse Model ◽  
B Cell ◽  
Knockout Mouse ◽  
Cell Development ◽  
B Cell Development ◽  
Conditional Knockout ◽  
Knockout Mouse Model ◽  
Conditional Knockout Mouse

514. THE REPRODUCTIVE PHENOTYPE OF THE IKKβ CONDITIONAL KNOCKOUT MOUSE

2009 ◽  
Vol 21 (9) ◽  
pp. 113
Author(s):  
A. Drummond ◽  
I. Kuyznierewicz ◽  
P. J. Fuller
Keyword(s):  
Granulosa Cells ◽  
Sertoli Cells ◽  
Knockout Mouse ◽  
Nuclear Translocation ◽  
Conditional Knockout ◽  
Mouse Line ◽  
Transgenic Mouse Line ◽  
Conditional Knockout Mouse ◽  
Iκb Kinase

Nuclear factor-κB (NF-κB) designates a family of transcription factors that have been shown to modulate antiviral, inflammatory and immune responses. Activation of NF-κB is dependent on IKKβ a component of the IκB kinase (IKK) complex which promotes degradation of IκB inhibitory proteins and allows nuclear translocation of NF-κB. Our studies in ovarian granulosa cell tumour cell lines (COV434 and KGN) indicate that NF-κB signalling is constitutively activated. FSH has been reported to increase XIAP expression through NFκB activity in granulosa cells, but beyond that the role of NFκB signalling in folliculogenesis has not been elucidated. To establish the significance of NF-κB signalling in the ovary (and testis), we have generated a gonadal specific IKKbeta conditional knockout mouse. A transgenic mouse line containing floxed IKKβ alleles (gift of M Karin, UCSD) was crossed with a cre mouse line (gift of M Matzuk, BCM) expressing the recombinase in anti-Müllerian hormone receptor expressing cells (granulosa cells or Sertoli cells). The resulting mice will not express IKKβ in granulosa cells or Sertoli cells and thus cannot activate the classical NFκB signalling pathway. On histological assessment, the ovaries and testes from flox x cre (heterogenous) mice appear normal with follicles of all developmental stages and corpora lutea. Preliminary data suggests that breeding with the heterogenous females resulted in increased litter sizes. The histology of the testes is also unremarkable. The mice homozygous for the deletion of IKKβ in the granulosa cells appear healthy and a preliminary assessment does not reveal gross morphological abnormalities of the ovaries. The results of detailed histological and overall assessment of these mice will be presented. These IKK conditional knockout mice should provide insights into the role of NFκB signalling in gonadal function.

scholarly journals CD300lf conditional knockout mouse reveals strain-specific cellular tropism for murine norovirus

2020 ◽  
Author(s):  
Vincent R. Graziano ◽  
Mia Madel Alfajaro ◽  
Cameron O. Schmitz ◽  
Renata B. Filler ◽  
Madison S. Strine ◽  
...  
Keyword(s):  
Knockout Mouse ◽  
Cell Types ◽  
Conditional Knockout ◽  
Cell Tropism ◽  
Murine Norovirus ◽  
Conditional Knockout Mouse ◽  
Tuft Cells ◽  
Cellular Tropism ◽  
Myelomonocytic Cells

Noroviruses are a leading cause of gastrointestinal infection in humans and mice. Understanding human norovirus (HuNoV) cell tropism has important implications for our understanding of viral pathogenesis. Murine norovirus (MNoV) is extensively used as a surrogate model for HuNoV. We previously identified CD300lf as the receptor for MNoV. Here, we generated a Cd300lf conditional knockout (CD300lfF/F) mouse to elucidate the cell tropism of persistent and non-persistent strains of murine norovirus. Using this mouse model, we demonstrate that CD300lf expression on intestinal epithelial cells (IECs), and on tuft cells in particular, is essential for transmission of the persistent MNoV strain CR6 (MNoVCR6) in vivo. In contrast, the non-persistent MNoV strain CW3 (MNoVCW3) does not require CD300lf expression on IECs for infection. However, deletion of CD300lf in myelomonocytic cells (LysM Cre+) partially reduces CW3 viral load in lymphoid and intestinal tissues. Disruption of CD300lf expression on B cells (CD19 Cre), neutrophils (Mrp8 Cre), and dendritic cells (CD11c Cre) did not affect MNoVCW3 viral RNA levels. Finally, we show that the transcription factor STAT1, which is critical for the innate immune response, partially restricts the cell tropism of MNoVCW3 to LysM+ cells. Taken together, these data demonstrate that CD300lf expression on tuft cells is essential for MNoVCR6, that myelomonocytic cells are a major, but not exclusive, target cell of MNoVCW3, and that STAT1 signaling restricts the cellular tropism of MNoVCW3. This provides the first genetic system to study the cell type-specific role of CD300lf in norovirus pathogenesis. IMPORTANCE Human noroviruses (HuNoVs) are a leading cause of gastroenteritis resulting in up to 200,000 deaths each year. The receptor and cell tropism of HuNoV in immunocompetent humans are unclear. We use murine norovirus (MNoV) as a model for HuNoV. We recently identified CD300lf as the sole physiologic receptor for MNoV. Here, we leverage this finding to generate a Cd300lf conditional knockout mouse to decipher the contributions of specific cell types to MNoV infection. We demonstrate that persistent MNoVCR6 requires CD300lf expression on tuft cells. In contrast, multiple CD300lf+ cell types, dominated by myelomonocytic cells, are sufficient for non-persistent MNoVCW3 infection. CD300lf expression on epithelial cells, B cells, neutrophils, and dendritic cells is not critical for MNoVCW3 infection. Mortality associated with MNoVCW3 strain in Stat1-/- mice does not require CD300lf expression on LysM+ cells, highlighting that both CD300lf receptor expression and innate immunity regulate MNoV cell tropism in vivo.

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