Background: The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression.
In spite of numerous, substantial advances in equine reproduction, many stages of embryonic and fetal morphological development are poorly understood, with no apparent single source of comprehensive information. Hence, the objective of the present study was to provide a complete macroscopic and microscopic description of the equine embryo/fetus at various gestational ages. Thirty-four embryos/fetuses were aged based on their crown rump length (CRL), and submitted to macroscopic description, biometry, light and scanning microscopy, as well as the alizarin technique. All observed developmental changes were chronologically ordered and described. As examples of the main observed features, an accentuated cervical curvature was observed upon macroscopic examination in all specimens. In the nervous system, the encephalic fourth ventricle and the encephalic vesicles forebrain, midbrain, and hindbrain, were visualized from Day 19 (ovulation = Day 0). The thoracic and pelvic limbs were also visualized; their extremities gave rise to the hoof during development from Day 27. Development of other structures such as pigmented optical vesicle, liver, tail, cardiac area, lungs, and dermal vascularization started on Days 25, 25, 19, 19, 34, and 35, respectively. Light and scanning microscopy facilitated detailed examinations of several organs, e.g., heart, kidneys, lungs, and intestine, whereas the alizarin technique enabled visualization of ossification. Observations in this study contributed to the knowledge regarding equine embryogenesis, and included much detailed data from many specimens collected over a long developmental interval.
During fetal development, mesenchymal progenitor (MP) cells are co-localized in major hematopoietic territories, such as yolk sac (YS), bone marrow (BM), liver (LV), and others. Studies using mouse and human MP cells isolated from fetus have shown that these cells are very similar but not identical to adult mesenchymal stem cells (MSC). Their differentiation potential is usually restricted to production of highly committed osteogenic and chondrogenic precursors. Such properties of fetal MP cells can be very useful for tissue regeneration, when a great number of committed precursors are required. The objectives of this study were to isolate and characterize MP cells from canine YS, BM, and LV in early and late stages of fetal development. Gestational stage was identified, and cell culture conditions were evaluated for efficient isolation of canine MP cells. All canine fetal MP cells expressed vimentin, nestin, and CD44 proteins. Cytokeratin 18 expression was observed in BM- and LV-MP cells, and vascular endothelial (VE)-cadherin expression was observed only in YS-MP cells. A small number of MP cells (5%) from LV and YS expressed Oct3/4 protein. The differentiation potential of canine fetal MP cells varied significantly: YS- and BM-MP cells differentiated into bone and cartilage, whereas LV-MP cells differentiation was limited to osteogenic fate. None of the canine fetal MP cells were able to differentiate into adipose cells. Our data suggest that canine fetal MP cells are an appropriate in vitro model to study MP biology from hematopoietic territories and they are a source of committed osteogenic and chondrogenic precursors for regenerative medicine.
Background: Placentas of guinea pig-related rodents are appropriate animal models for human placentation because of their striking similarities to those of humans. To optimize the pool of potential models in this context, it is essential to identify the occurrence of characters in close relatives.
Mammalian fetal survival and growth are dependent on a well-established and functional placenta. Although transient, the placenta is the first organ to be formed during pregnancy and is responsible for important functions during development, such as the control of metabolism and fetal nutrition, gas and metabolite exchange, and endocrine control. Epigenetic marks and gene expression patterns in early development play an essential role in embryo and fetal development. Specifically, the epigenetic phenomenon known as genomic imprinting, represented by the non-equivalence of the paternal and maternal genome, may be one of the most important regulatory pathways involved in the development and function of the placenta in eutherian mammals. A lack of pattern or an imprecise pattern of genomic imprinting can lead to either embryonic losses or a disruption in fetal and placental development. Genetically modified animals present a powerful approach for revealing the interplay between gene expression and placental function in vivo and allow a single gene disruption to be analyzed, particularly focusing on its role in placenta function. In this paper, we review the recent transgenic strategies that have been successfully created in order to provide a better understanding of the epigenetic patterns of the placenta, with a special focus on imprinted genes. We summarize a number of phenotypes derived from the genetic manipulation of imprinted genes and other epigenetic modulators in an attempt to demonstrate that gene-targeting studies have contributed considerably to the knowledge of placentation and conceptus development.
ABSTRACT. Duchenne muscular dystrophy (DMD) is a human disease characterized by progressive and irreversible skeletal muscle degeneration caused by mutations in genes coding for important muscle proteins. Unfortunately, there is no efficient treatment for this disease; it causes progressive loss of motor and muscular ability until death. The canine model (golden retriever muscular dystrophy) is similar to DMD, showing similar clinical signs. Fifteen dogs were followed from birth and closely observed for clinical signs. Dogs had their disease status confirmed by polymerase chain reaction analysis and genotyping. Clinical observations of musculoskeletal, morphological, gastrointestinal, respiratory, cardiovascular, and renal features allowed us to identify three distinguishable phenotypes in dystrophic dogs: mild (grade I), moderate (grade II) and severe (grade III). These three groups showed no difference in dystrophic alterations of muscle morphology and creatine kinase levels. This information will be useful for therapeutic trials, because DMD also shows significant, inter-and intra-familiar clinical variability. Additionally, being aware of phenotypic differences in this animal model is essential for correct interpretation and understanding of results obtained in pre-clinical trials.
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