Anatomy, physiological features, genetics and genetic alterations, breeding and strain differences relevant to the choice of the model—Impact of 3Rs

2022 ◽  
pp. 47-79
Author(s):  
Livia D'Angelo ◽  
Paolo de Girolamo ◽  
Laura Lossi ◽  
Adalberto Merighi ◽  
Marcello Raspa ◽  
...  
Keyword(s):  
Strain Differences ◽  
Genetic Alterations

scholarly journals Genetic variation responsible for mouse strain differences in integrin α2 expression is associated with altered platelet responses to collagen

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3396-3402 ◽  
Author(s):  
Tong-Tong Li ◽  
Susana Larrucea ◽  
Shiloe Souza ◽  
Suzanne M. Leal ◽  
José A. López ◽  
...  
Keyword(s):  
Human Platelet ◽  
Strain Differences ◽  
Genetic Alterations ◽  
Mouse Strains ◽  
Lag Phase ◽  
Lod Score ◽  
Log Odds ◽  
Integrin Α2 ◽  
Mouse System ◽  
Mouse Strain Differences

Abstract As mouse models have become commonplace for studying hemostasis and thrombosis, we considered whether the mouse system had utility for assessing genetic alterations in platelet receptors. Platelets from 5 mouse strains (C57BL/6 [C57], FVB/N [FVB], BALB/c, C3H/He, and 129Sv) showed only minor differences in the expression of integrin αIIb, integrin β3, glycoprotein (GP) Ibα, or GPVI across strains. However, FVB platelets expressed approximately 50% the level of integrin α2 as platelets from other strains (P < .0001). We bred FVB mice with C57 and assessed α2 expression in FVB/C57xFVB/C57 (F2) offspring. Linkage analysis demonstrated the gene responsible for α2 levels is tightly linked to the D13mit260 marker (log odds [lod] score 6.7) near the α2 gene. FVB platelets showed reduced aggregation and a longer lag phase to collagen. FVB and C57 platelets aggregated similarly to collagen-related peptide, but FVB platelets showed a reduction in rhodocytin-induced Syk and PLCγ2 tyrosine phosphorylation. Thus, FVB platelets express half the level of α2 as other mouse strains, a trait linked to the α2 gene and seemingly responsible for reduced platelet aggregation to collagen. These strain differences serve as a useful model for the 2-fold difference in human platelet α2β1 expression and demonstrate that α2β1 participates in signaling during platelet activation. (Blood. 2004;103:3396-3402)

High performance Nanogold™-in situ hybridzation and its use in the detection of hybridized and PCR-amplified microscopical preparations

1996 ◽  
Vol 54 ◽  
pp. 896-897
Author(s):  
G. W. Hacker ◽  
I. Zehbe ◽  
J. Hainfeld ◽  
A.-H. Graf ◽  
C. Hauser-Kronberger ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Messenger Rna ◽  
High Performance ◽  
Detection System ◽  
Direct Methods ◽  
Genetic Alterations ◽  
Chain Reaction ◽  
Protein Encoding ◽  
Polymerase Chain

In situ hybridization (ISH) with biotin-labeled probes is increasingly used in histology, histopathology and molecular biology, to detect genetic nucleic acid sequences of interest, such as viruses, genetic alterations and peptide-/protein-encoding messenger RNA (mRNA). In situ polymerase chain reaction (PCR) (PCR in situ hybridization = PISH) and the new in situ self-sustained sequence replication-based amplification (3SR) method even allow the detection of single copies of DNA or RNA in cytological and histological material. However, there is a number of considerable problems with the in situ PCR methods available today: False positives due to mis-priming of DNA breakdown products contained in several types of cells causing non-specific incorporation of label in direct methods, and re-diffusion artefacts of amplicons into previously negative cells have been observed. To avoid these problems, super-sensitive ISH procedures can be used, and it is well known that the sensitivity and outcome of these methods partially depend on the detection system used.

Molecular genetic markers for thyroid FNAB

2015 ◽  
Vol 54 (03) ◽  
pp. 94-100 ◽  
Author(s):  
P. B. Musholt ◽  
T. J. Musholt
Keyword(s):  
Genetic Markers ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Ultrasound Screening ◽  
Thyroid Malignancy ◽  
Thyroid Carcinomas ◽  
Molecular Genetic Markers ◽  
The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

Receptor tyrosine kinase gene amplification is predictive of intraoperative seizures during glioma resection with functional mapping

2020 ◽  
Vol 132 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
Bryan D. Choi ◽  
Daniel K. Lee ◽  
Jimmy C. Yang ◽  
Caroline M. Ayinon ◽  
Christine K. Lee ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Univariate Analysis ◽  
Tumor Resection ◽  
Tumor Grade ◽  
Molecular Data ◽  
Genetic Alterations ◽  
Functional Mapping ◽  
Chi Square ◽  
Kinase Gene ◽  
Glioma Resection

OBJECTIVEIntraoperative seizures during craniotomy with functional mapping is a common complication that impedes optimal tumor resection and results in significant morbidity. The relationship between genetic mutations in gliomas and the incidence of intraoperative seizures has not been well characterized. Here, the authors performed a retrospective study of patients treated at their institution over the last 12 years to determine whether molecular data can be used to predict the incidence of this complication.METHODSThe authors queried their institutional database for patients with brain tumors who underwent resection with intraoperative functional mapping between 2005 and 2017. Basic clinicopathological characteristics, including the status of the following genes, were recorded: IDH1/2, PIK3CA, BRAF, KRAS, AKT1, EGFR, PDGFRA, MET, MGMT, and 1p/19q. Relationships between gene alterations and intraoperative seizures were evaluated using chi-square and two-sample t-test univariate analysis. When considering multiple predictive factors, a logistic multivariate approach was taken.RESULTSOverall, 416 patients met criteria for inclusion; of these patients, 98 (24%) experienced an intraoperative seizure. Patients with a history of preoperative seizure and those treated with antiepileptic drugs prior to surgery were less likely to have intraoperative seizures (history: OR 0.61 [95% CI 0.38–0.96], chi-square = 4.65, p = 0.03; AED load: OR 0.46 [95% CI 0.26–0.80], chi-square = 7.64, p = 0.01). In a univariate analysis of genetic markers, amplification of genes encoding receptor tyrosine kinases (RTKs) was specifically identified as a positive predictor of seizures (OR 5.47 [95% CI 1.22–24.47], chi-square = 5.98, p = 0.01). In multivariate analyses considering RTK status, AED use, and either 2007 WHO tumor grade or modern 2016 WHO tumor groups, the authors found that amplification of the RTK proto-oncogene, MET, was most predictive of intraoperative seizure (p < 0.05).CONCLUSIONSThis study describes a previously unreported association between genetic alterations in RTKs and the occurrence of intraoperative seizures during glioma resection with functional mapping. Future models estimating intraoperative seizure risk may be enhanced by inclusion of genetic criteria.

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