Sodium channel Nav1.6 is up-regulated in the dorsal root ganglia in a mouse model of type 2 diabetes

2012 ◽  
Vol 87 (2-3) ◽  
pp. 244-249 ◽  
Author(s):  
Yan-Shun Ren ◽  
Nian-Song Qian ◽  
Yu Tang ◽  
Yong-Hui Liao ◽  
Yan-Ling Yang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Sodium Channel ◽  
Dorsal Root Ganglia ◽  
Dorsal Root

scholarly journals Activation of Raf signalling in NF2-null Schwann cells leads to sustained proliferation; an investigation of a new and inducible model for human schwannoma

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv7-iv7
Author(s):  
Charlotte Lespade ◽  
Liyam Laraba ◽  
Evyn Woodhouse ◽  
Marie Srotyr ◽  
Alison C Lloyd ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Mouse Model ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Proliferation Response

Abstract Aims The NF2 gene encodes the tumour suppressor Merlin, which is deleted in 100% of patients with the familial tumour predisposition syndrome neurofibromatosis type 2 but also in 70% of those who develop sporadic schwannomas. The Raf-TR mouse model uses a tamoxifen-inducible Raf-kinase/ oestrogen receptor fusion protein (Raf-TR) expressed in myelinating Schwann cells to mimic a nerve injury response in Schwann cell by activating Raf/MEK/ERK signalling in the absence of peripheral nerve injury. We will assess whether Raf/MEK/ERK activation on an NF2 null background leads to tumourigenesis within the vestibular nerves and dorsal root ganglia (DRGs), two tumour sites identified in the Periostin-Cre mouse model in which schwannoma formation is spontaneous, with a view to generating an inducible NF2 null schwannoma mouse model. Method Mice with a Schwann cell specific loss of Merlin were crossed with mice carrying a tamoxifen-inducible Raf-TR gene to generate Raf-TR+/-; P0-Cre+/-; NF2fl/fl (Cre+) mice which were NF2 null and compared to Raf-TR+/-; P0-Cre-/-; NF2fl/fl (Cre-) littermate controls. Mice were injected with tamoxifen or vehicle for five consecutive days and their vestibular nerves and dorsal root ganglia (DRGs) were analysed at various timepoints . An EdU proliferation assay was used to quantify the proliferation in the vestibular ganglia, as well as the DRGs. Rates of proliferation were compared to Cre- age-matched littermate controls treated with tamoxifen or vehicle. Results In the Periostin-Cre NF2 null schwannoma model, tumours form spontaneously in the DRGs and vestibular ganglia. In our new model, we see a clear increase in proliferation at 21 d post-injection in the NF2 null (Cre+) tamoxifen-treated mice compared to control (Cre-) tamoxifen-treated controls in both DRGs and vestibular ganglia. Cre- tamoxifen-treated mice do not show increased proliferation compared to Cre- vehicle controls. Taken together, this shows that activation of the Raf/MEK/ERK pathway in Schwann cells only causes a sustained proliferation response on an NF2 null background in the DRGs and vestibular ganglia. We are assessing later timepoints to further characterise tumour development in these mice. Conclusion Combining the Raf-TR mouse model to create a demyelinating phenotype with an NF2 null background leads to vastly increased rates of proliferation at the sites of schwannoma tumourigenesis within the peripheral nervous system: the DRGs and the vestibular ganglia. The high proliferation in the vestibular ganglia in particular is similar to the development of vestibular schwannomas in patients with Neurofibromatosis type 2. The new mouse model used in this study shows potential to be very useful as an inducible schwannoma tumour model, in which we can study the early events of tumour formation.

Structural analysis of tooth and jawbone in a type 2 diabetes mouse model

2014 ◽  
Author(s):  
Silvia Pabisch ◽  
Tsuguno Yamaguchi ◽  
Yasushi Koike ◽  
Kenji Egashira ◽  
Shinsuke Kataoka ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Structural Analysis ◽  
Mouse Model ◽  
Diabetes Mouse

Pharmacological Neprilysin Inhibition Improves Glucose Homeostasis in a Mouse Model of Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1825-P ◽  
Author(s):  
JACQUELINE H. PARILLA ◽  
STEVE MONGOVIN ◽  
BREANNE BARROW ◽  
NATHALIE ESSER ◽  
SAKENEH ZRAIKA
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Glucose Homeostasis ◽  
Neprilysin Inhibition

1734-P: High Dietary Fat Intake Exacerbates Insulin Resistance in a Type 2 Diabetes Genetic Mouse Model

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1734-P
Author(s):  
AUSTIN REILLY ◽  
SHIJUN YAN ◽  
ALEXA J. LONCHARICH ◽  
HONGXIA REN
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mouse Model ◽  
Dietary Fat ◽  
Fat Intake ◽  
Dietary Fat Intake ◽  
Genetic Mouse Model

scholarly journals Development of a Nongenetic Mouse Model of Type 2 Diabetes

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Elizabeth R. Gilbert ◽  
Zhuo Fu ◽  
Dongmin Liu
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mouse Model ◽  
Serum Insulin ◽  
Cell Mass ◽  
Low Fat ◽  
Β Cell ◽  
Islet Mass ◽  
Metabolic Characteristics

Insulin resistance and loss of β-cell mass cause Type 2 diabetes (T2D). The objective of this study was to generate a nongenetic mouse model of T2D. Ninety-six 6-month-old C57BL/6N males were assigned to 1 of 12 groups including (1) low-fat diet (LFD; low-fat control; LFC), (2) LFD with 1 i.p. 40 mg/kg BW streptozotocin (STZ) injection, (3), (4), (5), (6) LFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively, (7) high-fat diet (HFD), (8) HFD with 1 STZ injection, (9), (10), (11), (12) HFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively. After 4 weeks, serum insulin levels were reduced in HFD mice administered at least 2 STZ injections as compared with HFC. Glucose tolerance was impaired in mice that consumed HFD and received 2, 3, or 4 injections of STZ. Insulin sensitivity in HFD mice was lower than that of LFD mice, regardless of STZ treatment. Islet mass was not affected by diet but was reduced by 50% in mice that received 3 STZ injections. The combination of HFD and three 40 mg/kg STZ injections induced a model with metabolic characteristics of T2D, including peripheral insulin resistance and reduced β-cell mass.

Prevention of diet-induced type 2 diabetes in the C57BL/6J mouse model by an antidiabetic herbal formula

2003 ◽  
Vol 17 (1) ◽  
pp. 48-55 ◽  
Author(s):  
Yushu Huo ◽  
Wendell D. Winters ◽  
Da-lin Yao
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Herbal Formula

scholarly journals Expression of Alternatively Spliced Sodium Channel α-Subunit Genes

2004 ◽  
Vol 279 (44) ◽  
pp. 46234-46241 ◽  
Author(s):  
Christopher K. Raymond ◽  
John Castle ◽  
Philip Garrett-Engele ◽  
Christopher D. Armour ◽  
Zhengyan Kan ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Sodium Channel ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Genomic Sequence ◽  
Molecular Medicine ◽  
Primate Model ◽  
Α Subunit ◽  
Alternatively Spliced ◽  
Splicing Patterns

Molecular medicine requires the precise definition of drug targets, and tools are now in place to provide genome-wide information on the expression and alternative splicing patterns of any known gene. DNA microarrays were used to monitor transcript levels of the nine well-characterized α-subunit sodium channel genes across a broad range of tissues from cynomolgus monkey, a non-human primate model. Alternative splicing of human transcripts for a subset of the genes that are expressed in dorsal root ganglia, SCN8A (Nav1.6), SCN9A (Nav1.7), and SCN11A (Nav1.9) was characterized in detail. Genomic sequence analysis among gene family paralogs and between cross-species orthologs suggested specific alternative splicing events within transcripts of these genes, all of which were experimentally confirmed in human tissues. Quantitative PCR revealed that certain alternative splice events are uniquely expressed in dorsal root ganglia. In addition to characterization of human transcripts, alternatively spliced sodium channel transcripts were monitored in a rat model for neuropathic pain. Consistent down-regulation of all transcripts was observed, as well as significant changes in the splicing patterns of SCN8A and SCN9A.

scholarly journals Systemic and renal growth hormone–IGF1 axis involvement in a mouse model of type 2 diabetes

Diabetologia ◽  
2007 ◽  
Vol 50 (6) ◽  
pp. 1327-1334 ◽  
Author(s):  
Y. Segev ◽  
R. Eshet ◽  
O. Yakir ◽  
N. Haim ◽  
M. Phillip ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Hormone ◽  
Mouse Model ◽  
Renal Growth
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