Biomedical subjects

Joanna Sypecka

Publications and source records attributed to Joanna Sypecka.

4 recordsLinked to original sources

PubMed2006

Phenotypic diversity resulting from a point mutation.

Paralytic tremor (pt), a hereditary neurological disorder of rabbits, is a recessive, X-linked point mutation in exon 2 of the plp gene, responsible for substitution of 38 His by Glu in the PLP molecule. Pt genotype is expressed in a range of phenotypes, distinguished by the severity of neurological symptoms. Variable course of the disease, from totally asymptomatic to serious disorder, is observed even within the offspring of one breeding pair. The two most typical phenotypes have been chosen for the studies: one representing mild course of the disease and the other reflecting the most severe course. Since previous developmental studies proved that myelination is not only deficient but also delayed in pt rabbits, the age groups of animals have been selected with the aim of spanning the period of most active myelinogenesis. As revealed by experiments, the degree of CNS hypomyelination, which is the main future of pt mutation, is highest in the most affected animals. The amounts of mutated gene products, PLP and DM-20, examined both at mRNA and protein levels, exhibited a strong dependence on phenotype. Down-regulation of MBP and CNP was also observed. In contrast, MAG expression was normal or only slightly changed in mutants. The results lead to the conclusion that pt mutation in the plp gene affects a panel of events that governs myelinogenesis and is modulated in each individual that is manifested by gradation of neurological symptoms.

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PubMed2005

Banking of embryos of mutated, paralytic tremor rabbit by means of vitrification.

Cryopreservation enables banking of embryos for future use in medicine and in animal breeding. It also enables protection of germ plasm of endangered species and unique strains or lanes of laboratory animals. This paper describes an example of employing a vitrification method for banking of embryos of a unique lane of rabbit. The paralytic tremor (pt) rabbit is an X-linked recessive mutant lane of the Chinchilla breed characterized by hypomyelination of the central nervous system. In order to obtain a sufficient number of embryos, pt females were subjected to superovulation and surgical embryo collection. All suitable embryos were vitrified in 0.25 mL insemination straws in a modified EFS vitrification solution comprised of ethylene glycol (40%), Ficoll 70 (18%) and sucrose (0.3 M) in Hepes buffered TCM medium containing 20% fetal calf serum. In order to assess the efficiency of the vitrification procedure, a representative portion of vitrified embryos was warmed after a period of storage. Warmed embryos were subjected to in vitro culture for 72 h or were transferred to the uterus of synchronized recipients. The majority of the 141 warmed embryos survived vitrification and 100/141 (71%) developed to the blastocyst stage. Moreover, out of an additional 34 warmed embryos transferred to four recipients, eight (23.5%) developed to term and seven live pups were born. Six of the rabbit pups exhibited paralytic tremor symptoms typical for the pt lane. Although the overall efficiency of the vitrification method was lower compared with the effects usually achieved for 'healthy' embryos, results presented confirm the real possibility of the future restoration of the colony of pt rabbit, if sufficient number of embryos are cryopreserved.

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PubMed2005

Rabbit paralytic tremor phenotype--a plp1 gene mutation as a model of human Pelizaeus-Merzbacher disease.

The paralytic tremor (pt) disease in rabbits results from a point mutation in a plp gene and manifests itself by a broad range of neurological signs. Biochemical studies have shown that myelinogenesis is retarded and deficient in mutant rabbits. Myelin sheaths are usually thin and malformed. The number of oligodendrocytes is normal, however their differentiation and maturation is prolonged. The effects of the pt mutation were investigated in morphological, biochemical and molecular studies, resulting in the well-documented characteristics of the disease. The pt phenotype and its detailed characteristics make the mutated rabbit a good model of Pelizaeus-Merzbacher disease.

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PubMedDate not supplied

Different vulnerability to cytotoxicity and susceptibility to protection of progenitors versus mature oligodendrocytes.

Oligodendrocytes are known to be particularly vulnerable to the cytotoxic effect evoked by different neurodegenerative processes, such as ischemic insult, hypoxia, hypoglycemia or autoaggressive immunological attack like SM. They are the neural cells that undergo sophisticated process of maturation characterized by huge changes in cell metabolism and morphology. Small bipolar cells differentiate into multiprocessed mature oligodendrocytes capable of myelinating CNS. A question arises whether there are any differences in their sensitivity to excitotoxic events? To address this problem, the cells of two distinct stages of differentiation, i.e. progenitors (O-2A) and mature, myelinating oligodendrocytes (MBP+) were selected for investigation of the effects of such apoptogenic factors as H(2)O(2) or serum-withdrawal in vitro. Primary cultures obtained from the brain hemispheres of 18 days old Wistar rat embryos served after 10 days for the establishing pure oligodendrocyte culture (the "shake-off" method by McCarthy and de Vellis, 1980). Oligodendrocytes were cultured in DMEM with addition of insulin, transferrin and sodium selenite. Cytotoxic influence of selected apoptotic factors as well as neuroprotective effects of CsA were estimated by immunochemical detection. The obtained data suggest that progenitors and mature cells respond to apoptogenic conditions by activation of different molecular pathways and specific cytoprotective conditions should be worked out for each type of the cells.

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