Genetically modified mice- Methods, applications and outlook

Background & Aim: Transgenic mice, of tengenerated by random integration of foreign genes into the mouse genome or by targeted mutation in a particular gene, have demonstrated to be a very effective tool for studying gene function in living things. In this review article, we discussed on the current methods of generating genetically-modified mice and their related problems and then investigated the new methods developed to overcome these problems. Finally, we discussed future prospects on the gene targeting. Methods & Materials: This is a review article, which has been written after searching Pubmed, Scopus, Google Scholar, Springer, Elsevier and Magiran databases by using keywords of transgenic mice, functional genetics, genetargeting, and homologous recombination. Results: This study dealt with genetic variations in a wide range, differential processing and inactivation of gene-specific isoforms, local and induced genetic changes, Cre/loxP system and some future perspectives. Conclusion: Success rate in genetic modification of mouse genome has increased dramatically, and use of knockout mice has resulted in increased knowledge of human biology and diseases

Differentiation of human mesenchymal stem cells (MSC) to dopaminergic neurons: A comparison between Wharton's Jelly and olfactory mucosa as sources of MSCs

The generation of dopaminergic neurons from stem cells is a potential therapeutic approach to treat neurodegenerative disorders, such as Parkinson's disease. The current study aims to investigate the potential of two different types of mesenchymal stem cells derived from human Wharton's jelly and nasal cavity for differentiation into dopaminergic neurons. The differentiation capacities of both cell types were evaluated using real-time PCR, immunocytochemistry, flow cytometry and HPLC. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are noted for their capability to differentiate into mesodermal and non-mesodermal cells, including neurons. However, it was demonstrated that having the same neuroectodermal origin as the nervous system, the olfactory ectomesenchymal stem cells (OE-MSCs) expressed the neural marker MAP2 as well as dopaminergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT) and PITX3 to a greater extent than the WJ-MSCs both at the level of mRNA and protein. Furthermore, quantitative flow cytometric evaluation of these markers at 12 days post-induction supported the above-mentioned results. Finally, the assessment of the functionality of differentiated cells and their ability to synthesize dopamine measured by HPLC revealed that the OE-MSC-derived dopaminergic cells released almost the same amount of dopamine as that secreted by WJ-MSC-derived cells. Thus it showed the difference in their functionality to be negligible. Overall, it may be concluded that higher proliferation and differentiation capacity of OE-MSCs, along with their easier harvestability and autologous transplantability compared with WJ-MSCs, makes them a better cell source for stem cell therapy of neurodegenerative disorders which are caused by degeneration of dopaminergic neurons. © 2019 Elsevier B.V