Novel spontaneous myelodysplastic syndrome mouse model

Abstract

Background Myelodysplastic syndrome (MDS) is a group of disorders involving hemopoietic dysfunction leading to leukemia. Although recently progress has been made in identifying underlying genetic mutations, many questions still remain. Animal models of MDS have been produced by introduction of specific mutations. However, there is no spontaneous mouse model of MDS, and an animal model to simulate natural MDS pathogenesis is urgently needed. Methods In characterizing the genetically diverse mouse strains of the Collaborative Cross (CC) we observed that one, designated JUN, had abnormal hematological traits. This strain was thus further analyzed for phenotypic and pathological identification, comparing the changes in each cell population in peripheral blood and in bone marrow. Results In a specific‐pathogen free environment, mice of the JUN strain are relatively thin, with healthy appearance. However, in a conventional environment, they become lethargic, develop wrinkled yellow hair, have loose and light stools, and are prone to infections. We found that the mice were cytopenic, which was due to abnormal differentiation of multipotent bone marrow progenitor cells. These are common characteristics of MDS. Conclusions A mouse strain, JUN, was found displaying spontaneous myelodysplastic syndrome. This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models. JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.

Morphine analgesia in male inbred genetic diversity mice recapitulates the among‐individual variance in response to morphine in humans

“…15,16 Susceptibility to diseases, development of the animal model, and related genetic loci mapping are being investigated increasingly in CC mice. [17][18][19] In our research, we found that different strains of GD mice exhibit an extremely wide range of variance in response to morphine analgesia, including large differences in morphine sensitivity and susceptibility of morphine tolerance.…”

“…After more than 10 years of breeding, the resulting inbred CC strains exhibit a wide range of traits and have great advantages in integrative analysis of complex systems that can be defined only in vivo, such as resistance to Ebola virus infection and variability in immunoglobulin glycosylation 15,16 . Susceptibility to diseases, development of the animal model, and related genetic loci mapping are being investigated increasingly in CC mice 17–19 . In our research, we found that different strains of GD mice exhibit an extremely wide range of variance in response to morphine analgesia, including large differences in morphine sensitivity and susceptibility of morphine tolerance.…”

Gut microbiome and serum amino acid metabolome alterations in autism spectrum disorder

“…The double-stranded PCR products were heat-denatured and circularized by the splint oligo sequence. The single-strand circle DNA (ssCir DNA) was formatted as the final library and qualified by QC 22 . The qualified libraries were sequenced on the MGISEQ-2000 platform (BGI Shenzhen, China).…”

In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression

“…Even though animal models are valuable tools for research, the expenditure is high, drug screening requires a large amount of animals and, biologically, model animals cannot completely mimic human BM microenvironments. These issues emphasize the need for better strategies to improve human systems modeling in vivo; in this context, new results and extensive reviews regarding animal models for leukemic research are periodically published [127,129,[136][137][138][139][140][141][142][143][144][145][146]. The graph is based on [129], with additional information from [145,[147][148][149].…”