FISH Mapping of Two Putative Keratin Gene Clusters on Cat (Felis catus) Chromosomes

Genes encoding keratins are evolutionary highly conserved and clustered in two linkage groups in mammalian genomes. Canine keratin 9 (K-9) and keratin 2e (K-2) cosmid-derived gene probes were used to localize the acidic and basic-neutral keratin gene clusters to cat chromosomes E1q12 and B4q15, respectively. The status of the physical map of the cat genome is discusse

Canine-Derived Cosmid Probes Containing Microsatellites Can Be Used in Physical Mapping of Arctic Fox (Alopex lagopus) and Chinese Raccoon Dog (Nyctereutes procyonoides procyonoides) Genomes

Rapid development of the canine marker genome map facilitates genome mapping of other Canidae species. In this study we present chromosomal localization of 18 canine-derived cosmid probes containing microsatellites in the arctic fox (Alopex lagopus) and Chinese raccoon dog (Nyctereutes procyonoides procyonoides) genomes by the use of fluorescence in situ hybridization (FISH). The chromosome localizations in the arctic fox are in general agreement with data obtained from comparative genome maps of the dog and the fox. However, our studies showed that the order of the loci on some chromosomes was changed during karyotype evolution. Therefore, we suggest that small intrachromosomal rearrangements took plac

Testiculaire aandoening van seksuele differentiatie (78,XX SRY-negatief) bij een vrouwelijke Franse buldog

A presumably female intact French bulldog of ten months old was presented to the Faculty of Veterinary Medicine of the Ghent University with an enlarged clitoris and purulent vaginal discharge. It was suggested to remove the enlarged clitoris as to avoid further irritation and to perform a gonadectomy at the same time, since the owners were not planning to breed with the dog. An abnormal reproductive tract was observed during surgery. A normal uterus was present, but both gonads resembled testes. Histologic examination of the resected tissues confirmed the presence of bilateral testes in combination with a normal uterus. Karyotyping and molecular analysis of the SRY-gene resulted in a 78,XX SRY-negative karyotype. The French bulldog was diagnosed with a 78,XX SRY-negative testicular disorder of sex development (DSD)

Mouse polyQ database: a new online resource for research using mouse models of neurodegenerative diseases

BACKGROUND: The polyglutamine (polyQ) family of disorders comprises 9 genetic diseases, including several types of ataxia and Huntington disease. Approximately two decades of investigation and the creation of more than 130 mouse models of polyQ disorders have revealed many similarities between these diseases. The disorders share common mutation types, neurological characteristics and certain aspects of pathogenesis, including morphological and physiological neuronal alterations. All of the diseases still remain incurable. DESCRIPTION: The large volume of information collected as a result of the investigation of polyQ models currently represents a great potential for searching, comparing and translating pathogenesis and therapeutic information between diseases. Therefore, we generated a public database comprising the polyQ mouse models, phenotypes and therapeutic interventions tested in vivo. The database is available at http://conyza.man.poznan.pl/. CONCLUSION: The use of the database in the field of polyQ diseases may accelerate research on these and other neurodegenerative diseases and provide new perspectives for future investigation

Effect of three common SNPs in 5′-flanking region of LEP and ADIPOQ genes on their expression in Polish obese children and adolescents

Genes encoding adipokines are considered as candidates for human obesity. In this study we analyzed the expression of leptin (LEP) and adiponectin (ADIPOQ) genes in relation to common 5′-flanking or 5′UTR variants: -2548G>A (LEP), 19A>G (LEP) and -11377C>G (ADIPOQ) in Polish obese children and adolescents. Relative transcription levels in the subcutaneous adipose tissue (real time RT–PCR) and serum protein concentrations (RIA) were measured in 48 obese subjects with known genotypes at three polymorphic sites and in five non-obese controls. None of the studied polymorphisms altered significantly the expression. Significantly elevated relative transcription levels of the LEP gene (P < 0.05) and serum leptin concentrations (P < 0.01) were recorded in obese patients, when compared with the non-obese controls, but such differences were not found for the ADIPOQ gene. Interestingly, the leptin to adiponectin protein concentration ratio (L/A) was approximately sevenfold higher in obese children and adolescents when compared with the non-obese controls (P < 0.001). Taking into consideration the observed relationship between the genotypes and the gene expression level we suggest that these SNPs are not conclusive markers for predisposition to obesity in Polish children and adolescents. On the other hand, we confirmed that the leptin to adiponectin gene expression ratio (L/A) is an informative index characterizing obesity

An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases

<p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) and antisense strategies provide experimental therapeutic agents for numerous diseases, including polyglutamine (polyQ) disorders caused by CAG repeat expansion. We compared the potential of different oligonucleotide-based strategies for silencing the genes responsible for several polyQ diseases, including Huntington's disease and two spinocerebellar ataxias, type 1 and type 3. The strategies included nonallele-selective gene silencing, gene replacement, allele-selective SNP targeting and CAG repeat targeting.</p> <p>Results</p> <p>Using the patient-derived cell culture models of polyQ diseases, we tested various siRNAs, and antisense reagents and assessed their silencing efficiency and allele selectivity. We showed considerable allele discrimination by several SNP targeting siRNAs based on a weak G-G or G-U pairing with normal allele and strong G-C pairing with mutant allele at the site of RISC-induced cleavage. Among the CAG repeat targeting reagents the strongest allele discrimination is achieved by miRNA-like functioning reagents that bind to their targets and inhibit their translation without substantial target cleavage. Also, morpholino analog performs well in mutant and normal allele discrimination but its efficient delivery to cells at low effective concentration still remains a challenge.</p> <p>Conclusions</p> <p>Using three cellular models of polyQ diseases and the same experimental setup we directly compared the performance of different oligonucleotide-based treatment strategies that are currently under development. Based on the results obtained by us and others we discussed the advantages and drawbacks of these strategies considering them from several different perspectives. The strategy aimed at nonallele-selective inhibiting of causative gene expression by targeting specific sequence of the implicated gene is the easiest to implement but relevant benefits are still uncertain. The gene replacement strategy that combines the nonallele-selective gene silencing with the expression of the exogenous normal allele is a logical extension of the former and it deserves to be explored further. Both allele-selective RNAi approaches challenge cellular RNA interference machinery to show its ability to discriminate between similar sequences differing in either single base substitutions or repeated sequence length. Although both approaches perform well in allele discrimination most of our efforts are focused on repeat targeting due to its potentially higher universality.</p

Mouse Models of Polyglutamine Diseases in Therapeutic Approaches: Review and Data Table. Part II

Mouse models of human diseases are created both to understand the pathogenesis of the disorders and to find successful therapies for them. This work is the second part in a series of reviews of mouse models of polyglutamine (polyQ) hereditary disorders and focuses on in vivo experimental therapeutic approaches. Like part I of the polyQ mouse model review, this work is supplemented with a table that contains data from experimental studies of therapeutic approaches in polyQ mouse models. The aim of this review was to characterize the benefits and outcomes of various therapeutic strategies in mouse models. We examine whether the therapeutic strategies are specific to a single disease or are applicable to more than one polyQ disorder in mouse models. In addition, we discuss the suitability of mouse models in therapeutic approaches. Although the majority of therapeutic studies were performed in mouse models of Huntington disease, similar strategies were also used in other disease models. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12035-012-8316-3) contains supplementary material, which is available to authorized users

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases