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Mammalian Genome: Official Journal of the International Mammalian Genome Society

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https://read.qxmd.com/read/30847553/humanized-mouse-models-of-immunological-diseases-and-precision-medicine
#1
REVIEW
Leonard D Shultz, James Keck, Lisa Burzenski, Sonal Jangalwe, Shantashri Vaidya, Dale L Greiner, Michael A Brehm
With the increase in knowledge resulting from the sequencing of the human genome, the genetic basis for the underlying differences in individuals, their diseases, and how they respond to therapies is starting to be understood. This has formed the foundation for the era of precision medicine in many human diseases that is beginning to be implemented in the clinic, particularly in cancer. However, preclinical testing of therapeutic approaches based on individual biology will need to be validated in animal models prior to translation into patients...
March 7, 2019: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30843090/analysis-and-preliminary-validation-of-the-molecular-mechanism-of-fat-deposition-in-fatty-and-lean-pigs-by-high-throughput-sequencing
#2
Jing Xiang Cui, Qi Fan Zeng, Wei Chen, Hong Zhang, Yong Qing Zeng
Fat deposition in muscle includes intramuscular fat (IMF) and intermuscular fat. IMF content is an index of pork quality; however, because IMF content is difficult to measure in vivo in young animals, conventional breeding for IMF content is difficult to carry out. The mechanism and progression of animal fat deposition is not well understood, and there are currently no effective control methods. In this study, using Laiwu and large white pigs as the research subjects and RNA sequencing technology, we analyzed the genetic mechanism of animal fat deposition in pigs...
March 6, 2019: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30820643/treating-rett-syndrome-from-mouse-models-to-human-therapies
#3
REVIEW
Neeti Vashi, Monica J Justice
Rare diseases are very difficult to study mechanistically and to develop therapies for because of the scarcity of patients. Here, the rare neuro-metabolic disorder Rett syndrome (RTT) is discussed as a prototype for precision medicine, demonstrating how mouse models have led to an understanding of the development of symptoms. RTT is caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). Mecp2-mutant mice are being used in preclinical studies that target the MECP2 gene directly, or its downstream pathways...
February 28, 2019: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30788588/evidence-for-a-de-novo-dominant-germ-line-mutation-causative-of-osteogenesis-imperfecta-in-two-red-angus-calves
#4
Jessica L Petersen, Shauna M Tietze, Rachel M Burrack, David J Steffen
A genetic disorder, osteogenesis imperfecta (OI) is broadly characterized by connective tissue abnormalities and bone fragility most commonly attributed to alterations in Type I collagen. Two Red Angus calves by the same sire presented with severe bone and dental fragility, blue sclera, and evidence of in utero fractures consistent with OI congenita. Comparative analyses with human cases suggested the OI in these calves most closely resembled that classified as OI Type II. Due to the phenotypic classification and shared paternity, a dominant, germ-line variant was hypothesized as causative although recessive genotypes were also considered due to a close relationship between the sire and dam of one calf...
February 20, 2019: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30778664/genetic-variation-in-thyroid-folliculogenesis-influences-susceptibility-to-hypothyroidism-induced-hearing-impairment
#5
Amanda H Mortensen, Qing Fang, Michelle T Fleming, Thomas J Jones, Alexandre Z Daly, Kenneth R Johnson, Sally A Camper
Maternal and fetal sources of thyroid hormone are important for the development of many organ systems. Thyroid hormone deficiency causes variable intellectual disability and hearing impairment in mouse and man, but the basis for this variation is not clear. To explore this variation, we studied two thyroid hormone-deficient mouse mutants with mutations in pituitary-specific transcription factors, POU1F1 and PROP1, that render them unable to produce thyroid stimulating hormone. DW/J-Pou1f1dw/dw mice have profound deafness and both neurosensory and conductive hearing impairment, while DF/B-Prop1df/df mice have modest elevations in hearing thresholds consistent with developmental delay, eventually achieving normal hearing ability...
February 18, 2019: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30600355/fearful-old-world-a-commentary-on-the-second-international-summit-on-human-genome-editing
#6
REVIEW
Andy Greenfield
Genome editing is revolutionising our ability to modify genomes with exquisite precision for medical and agricultural applications, and in basic research. The first International Summit on Human Genome Editing, organised jointly by the US National Academies of Sciences and Medicine, the Chinese Academy of Sciences and the UK Royal Society, was held in Washington DC at the end of 2015. Its aim was to explore scientific, legal and ethical perspectives on the prospective use of human genome editing as a therapeutic intervention in disease (so-called somatic genome editing) and as a possible intervention in human reproduction (so-called germ-line genome editing)...
January 2, 2019: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30591971/a-deletion-in-the-ctns-gene-causes-renal-tubular-dysfunction-and-cystine-accumulation-in-lea-tohm-rats
#7
Yukiko Shimizu, Rieko Yanobu-Takanashi, Kenta Nakano, Kenji Hamase, Toshiaki Shimizu, Tadashi Okamura
The Long-Evans Agouti (LEA/Tohm) rat has recently been established as a new rat model of type 2 diabetes. The onset of diabetes mellitus was observed only in male LEA/Tohm rats; however, urinary glucose appeared before the onset of diabetes. To clarify the genetic basis of urinary glucose, we performed genetic linkage analysis using (BN × LEA) F2 intercross progeny. A recessively acting locus responsible for urinary glucose excretion (ugl) was mapped to a 7.9 Mb region of chromosome 10, which contains the cystinosin (Ctns) gene...
December 27, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30515527/correction-to-quantitative-trait-mapping-in-diversity-outbred-mice-identifies-two-genomic-regions-associated-with-heart-size
#8
John R Shorter, Wei Huang, Ju Youn Beak, Kunjie Hua, Daniel M Gatti, Fernando Pardo-Manuel de Villena, Daniel Pomp, Brian C Jensen
The original article has been published with an incorrect text in Materials and Methods section. The corrected text should read as.
December 4, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30506450/a-mir-18a-binding-site-polymorphism-in-cdc42-3-utr-affects-cdc42-mrna-expression-in-placentas-and-is-associated-with-litter-size-in-pigs
#9
Ruize Liu, Dadong Deng, Xiangdong Liu, Yujing Xiao, Ji Huang, Feiyu Wang, Xinyun Li, Mei Yu
Increasing evidence suggests that miRNA binding-site polymorphism in the 3'-untranslated region (3'UTR) of a target gene could affect that gene's expression, and can be associated with a variety of complex traits. In this study, we find that miR-18a and cell division cycle 42 (CDC42) mRNA, whose expression was inversely correlated, are differentially expressed in porcine placentas during critical stages of placental development. rs55618224 (T>C), a SNP in the 3'UTR region of CDC42 that is perfectly complementary to the miR-18a seed could influence miR-18a-related regulation of CDC42 gene by altering their binding affinity...
December 1, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30446791/perspective-cancer-vaccines-in-the-era-of-immune-checkpoint-blockade
#10
REVIEW
Jonathan Cebon
Current excitement about cancer immunotherapy is the result of unprecedented clinical impact from immune checkpoint inhibitors, particularly those that target programmed death (PD)-1 and PD-ligand (L)-1. Numerous other immunotherapeutics are also finding their way into the clinic either alone or in combination, and these have potential applications in many cancer types. Therapeutic cancer vaccines have been a major focus for many pioneers in the field yet have largely failed to live up to expectations as game-changing immunotherapeutics...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30390107/introduction-to-mammalian-genome-special-issue-inflammation-and-immunity-in-cancer
#11
EDITORIAL
Andreas Behren, Daniel Speidel, George Kollias, Viive M Howell
No abstract text is available yet for this article.
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30225648/lessons-learnt-from-the-tasmanian-devil-facial-tumour-regarding-immune-function-in-cancer
#12
REVIEW
Emma Peel, Katherine Belov
Genetic and genomic technologies have facilitated a greater understanding of the Tasmanian devil immune system and the origins, evolution and spread of devil facial tumour disease (DFTD). DFTD is a contagious cancer that has caused significant declines in devil populations across Tasmania. Immune responses to DFTD are rarely detected, allowing the cancer to pass between individuals and proliferate unimpeded. Early immunosenscence in devils appears to decrease anti-tumour immunity in older animals compared to younger animals, which may increase susceptibility to DFTD and explain high DFTD prevalence in this age group...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30182300/thymocyte-self-renewal-and-oncogenic-risk-in-immunodeficient-mouse-models-relevance-for-human-gene-therapy-clinical-trials-targeting-haematopoietic-stem-cell-populations
#13
REVIEW
Samantha L Ginn, Matthew P McCormack, Ian E Alexander
Emerging evidence indicates that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Here we discuss formative studies demonstrating that, in mice, early thymocytes acquire self-renewing potential when thymic progenitor supply is sub-physiological and the importance of cellular competition with this at-risk cell population to prevent lymphoid malignancy. We also consider the possibility that increased thymic residency time, established under conditions of limited cellular competition, may have contributed to oncogenesis observed in early SCID-X1 trials when combined with insertional activation of proto-oncogenes such as LMO2...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30178306/roles-of-cytotoxic-and-helper-innate-lymphoid-cells-in-cancer
#14
REVIEW
Camille Guillerey
Natural killer (NK) cells have long been recognized for their anti-cancer activity and are now included in the large family of innate lymphoid cells (ILCs). The discovery of new ILC subsets that, similarly to NK cells, are able to kill tumor cells encourages us to redefine NK cell role in anti-tumor immunity. Conventional NK cells circulate through the blood and screen the body for "stressed" cells. Therefore, NK cells are believed to play a key role in cancer immunosurveillance by the early elimination of cells undergoing malignant transformation...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30178305/radiation-inflammation-and-the-immune-response-in-cancer
#15
REVIEW
Kelly J McKelvey, Amanda L Hudson, Michael Back, Tom Eade, Connie I Diakos
Radiation is an important component of cancer treatment with more than half of all patients receive radiotherapy during their cancer experience. While the impact of radiation on tumour morphology is routinely examined in the pre-clinical and clinical setting, the impact of radiation on the tumour microenvironment and more specifically the inflammatory/immune response is less well characterised. Inflammation is a key contributor to short- and long-term cancer eradication, with significant tumour and normal tissue consequences...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30178304/b-cells-and-antibody-production-in-melanoma
#16
REVIEW
Jessica Da Gama Duarte, Janique M Peyper, Jonathan M Blackburn
Recent developments in the immuno-oncology field strongly support a role for the immune system in both the prevention and progression of melanoma. Melanoma is a highly immunogenic cancer, including its ability to induce tumour antigen-specific B cell and antibody responses through largely unknown mechanisms. This review considers likely hypothetical mechanisms by which anti-tumour surveillance detects pre-cancerous cells and by which immune (including B cell and antibody) responses may be elicited during malignancy...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30167844/identifying-neoantigens-for-use-in-immunotherapy
#17
REVIEW
Sharon Hutchison, Antonia L Pritchard
This review focuses on the types of cancer antigens that can be recognised by the immune system and form due to alterations in the cancer genome, including cancer testis, overexpressed and neoantigens. Specifically, neoantigens can form when cancer cell-specific mutations occur that result in alterations of the protein from 'self'. This type of antigen can result in an immune response sufficient to clear tumour cells when activated. Furthermore, studies have reported that the likelihood of successful immunotherapeutic targeting of cancer by many different methods was reliant on immune response to neoantigens...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30132062/interaction-of-pvr-pvrl2-with-tigit-dnam-1-as-a-novel-immune-checkpoint-axis-and-therapeutic-target-in-cancer
#18
REVIEW
Hauke Stamm, Jasmin Wellbrock, Walter Fiedler
Avoiding immune surveillance and inducing a tumor-promoting inflammatory milieu found entry into the new generation of the hallmarks of cancer. Cancer cells hijack immune mechanisms which physiologically protect the body from the development of autoimmune diseases and excessive tissue damage during inflammation by downregulating immune responses. This is frequently achieved by upregulation of immune checkpoints. Therefore, the blocking of immune checkpoint ligand-receptor interactions can reinstall the immune systems capability to fight cancer cells as shown for CTLA4 and PD-1 inhibitors in a clinical setting...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30062485/the-intertwined-fates-of-inflammation-and-coagulation-in-glioma
#19
REVIEW
Angela Cho, Kelly J McKelvey, Adrian Lee, Amanda L Hudson
Inflammation and coagulation are two intertwined pathways with evolutionary ties being traced back to the hemocyte, a single cell type in invertebrates that has functions in both the inflammatory and coagulation pathways. These systems have functioned together throughout evolution to provide a solid defence against infection, damaged cells and irritants. While these systems work in harmony the majority of the time, they can also become dysregulated or corrupted by tumours, enhancing tumour proliferation, invasion, dissemination and survival...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://read.qxmd.com/read/30046851/the-role-of-proteomics-in-the-age-of-immunotherapies
#20
REVIEW
Sarah A Hayes, Stephen Clarke, Nick Pavlakis, Viive M Howell
The antigenic landscape of the adaptive immune response is determined by the peptides presented by immune cells. In recent years, a number of immune-based cancer therapies have been shown to induce remarkable clinical responses through the activation of the patient's immune system. As a result, there is a need to identify immune biomarkers capable of predicting clinical response. Recent advances in proteomics have led to considerable developments in the more comprehensive profiling of the immune response. "Immunoproteomics" utilises a rapidly increasing collection of technologies in order to identify and quantify antigenic peptides or proteins...
December 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
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