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The Journal of Veterinary Medical... Aug 2014Ataxic rolling Nagoya (PROD-rol/rol) mice, which carry a mutation in the α1 subunit of the Cav2.1 channel (Cacna1a) gene, were discovered in 1969. They show white spots...
Ataxic rolling Nagoya (PROD-rol/rol) mice, which carry a mutation in the α1 subunit of the Cav2.1 channel (Cacna1a) gene, were discovered in 1969. They show white spots on agouti coat and have a mutation in the piebald spotting (s) locus. However, mutation analysis of the s locus encoding the endothelin receptor type B (Ednrb) gene in PROD-rol/rol mice had not been performed. Here, we examined the genomic and mRNA sequences of the Ednrb gene in PROD-rol/rol and wild-type rolling Nagoya (PROD-s/s) and studied the expression patterns of Ednrb and Cacna1a genes in these mice in comparison with C57BL/6J mice. Polymerase chain reaction analyses revealed two silent nucleotide substitutions in the coding region and insertion of a retroposon-like element in intron 1 of the Ednrb gene. Expression analyses demonstrated similar localizations and levels of Ednrb and Cacna1a expression in the colon between PROD-rol/rol and PROD-s/s mice, but the expression levels of both genes were diminished compared with C57BL/6J mice. Microsatellite genotyping showed that at least particular regions of chromosome 14 proximal to the Ednrb locus of the PROD strain were derived from Japanese fancy piebald mice. These results indicated that PROD-rol/rol mice have two mutant genes, Ednrb and Cacna1a. As no PROD strain had an intact Ednrb gene, using congenic rolling mice would better serve to examine rolling Nagoya-type Cav2.1 channel dysfunctions.
Topics: Animals; Calcium Channels, N-Type; Colon; DNA Mutational Analysis; DNA Primers; In Situ Hybridization; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Microsatellite Repeats; Phenotype; Piebaldism; Real-Time Polymerase Chain Reaction; Receptor, Endothelin B; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 24758835
DOI: 10.1292/jvms.14-0096 -
Indian Journal of Dermatology,... 2014
Topics: Adolescent; Family Health; Female; Humans; India; Male; Melanosis; Pedigree; Piebaldism
PubMed: 24685861
DOI: 10.4103/0378-6323.129404 -
The Journal of Biological Chemistry Apr 2014The small GTPase Rab27A is a crucial regulator of actin-based melanosome transport in melanocytes, and functionally defective Rab27A causes human Griscelli syndrome type...
The GTPase-deficient Rab27A(Q78L) mutant inhibits melanosome transport in melanocytes through trapping of Rab27A effector protein Slac2-a/melanophilin in their cytosol: development of a novel melanosome-targetinG tag.
The small GTPase Rab27A is a crucial regulator of actin-based melanosome transport in melanocytes, and functionally defective Rab27A causes human Griscelli syndrome type 2, which is characterized by silvery hair. A GTPase-deficient, constitutively active Rab27A(Q78L) mutant has been shown to act as an inhibitor of melanosome transport and to induce perinuclear aggregation of melanosomes, but the molecular mechanism by which Rab27A(Q78L) inhibits melanosome transport remained to be determined. In this study, we attempted to identify the primary cause of the perinuclear melanosome aggregation induced by Rab27A(Q78L). The results showed that Rab27A(Q78L) is unable to localize on mature melanosomes and that its inhibitory activity on melanosome transport is completely dependent on its binding to the Rab27A effector Slac2-a/melanophilin. When we forcibly expressed Rab27A(Q78L) on mature melanosomes by using a novel melanosome-targeting tag that we developed in this study and named the MST tag, the MST-Rab27A(Q78L) fusion protein behaved in the same manner as wild-type Rab27A. It localized on mature melanosomes without inducing melanosome aggregation and restored normal peripheral melanosome distribution in Rab27A-deficient cells. These findings indicate that the GTPase activity of Rab27A is required for its melanosome localization but is not required for melanosome transport.
Topics: Adaptor Proteins, Signal Transducing; Amino Acid Substitution; Animals; COS Cells; Chlorocebus aethiops; Humans; Immunologic Deficiency Syndromes; Lymphohistiocytosis, Hemophagocytic; Melanosomes; Mice; Mutation, Missense; Piebaldism; Primary Immunodeficiency Diseases; Protein Transport; rab GTP-Binding Proteins; rab27 GTP-Binding Proteins
PubMed: 24584932
DOI: 10.1074/jbc.M114.552281 -
Microsurgery May 2014We previously demonstrated recipient-derived neoangiogenesis to maintain viability of living bone allogeneic transplants without long-term immunosuppression. The effect...
We previously demonstrated recipient-derived neoangiogenesis to maintain viability of living bone allogeneic transplants without long-term immunosuppression. The effect of cytokine delivery to enhance this process is studied. Vascularized femur transplantation was performed from Dark Agouti to Piebald Virol Glaxo rats. Poly(d,l-lactide-co-glycolide) microspheres loaded with buffer (N = 11), basic fibroblast growth factor (FGF2) (N = 10), vascular endothelial growth factor (VEGF) (N = 11), or both (N = 11) were inserted intramedullarly alongside a recipient-derived arteriovenous bundle. FK-506 was administered for 2 weeks. At 18 weeks, bone blood flow, microangiography, histologic, histomorphometric, and alkaline phosphatase measurements were performed. Bone blood flow was greater in the combined group than control and VEGF groups (P = 0.04). Capillary density was greater in the FGF2 group than in the VEGF and combined groups (P < 0.05). Bone viability, growth, and alkaline phosphatase activity did not vary significantly between groups. Neoangiogenesis in vascularized bone allotransplants is enhanced by angiogenic cytokine delivery, with results using FGF2 that are comparable to isotransplant from previous studies. Further studies are needed to achieve bone formation similar to isotransplants.
Topics: Animals; Bone Development; Bone Transplantation; Bone and Bones; Female; Fibroblast Growth Factor 2; Neovascularization, Physiologic; Osteogenesis; Rats; Time Factors; Vascular Endothelial Growth Factor A
PubMed: 24395434
DOI: 10.1002/micr.22221 -
Postepy Higieny I Medycyny... Nov 2013Hypo- and hyperpigmentation disorders are the most severe dermatological diseases observed in patients from all over the world. These disorders can be divided into... (Review)
Review
Hypo- and hyperpigmentation disorders are the most severe dermatological diseases observed in patients from all over the world. These disorders can be divided into melanoses connected with disorders of melanocyte function and melanocytoses connected with melanocyte development. The article presents some hereditary hypomelanocytoses, which are caused by abnormal melanoblast development, migration and proliferation as well as by abnormal melanocyte viability and proliferation. These disorders are represented by Waardenburg syndrome, piebaldism and Tietz syndrome, and are caused by different mutations of various or the same genes. The types of mutations comprise missense and nonsense mutations, frameshifts (in-frame insertions or deletions), truncating variations, splice alterations and non-stop mutations. It has been demonstrated that mutations of the same gene may cause different hypopigmentation syndromes that may have similar phenotypes. For example, mutations of the MITF gene cause Waardenburg syndrome type 2A as well as Tietz syndrome. It has also been demonstrated that mutations of different genes may cause an identical syndrome. For example, mutations of MITF, SNAI2 and SOX10 genes are observed in Waardenburg syndrome type II and mutations of EDNRB, EDN3 and SOX10 genes are responsible for Waardenburg syndrome type IV. In turn, mutation of the KIT gene and/or heterozygous deletion of the SNAI2 gene result in piebaldism disease. The knowledge of the exact mechanisms of pigmentary disorders may be useful in the development of new therapeutic approaches to their treatment.
Topics: Albinism, Oculocutaneous; Deafness; Endothelin-3; Heterozygote; Humans; Microphthalmia-Associated Transcription Factor; Mutation; PAX3 Transcription Factor; Paired Box Transcription Factors; Phenotype; Piebaldism; Proto-Oncogene Proteins c-kit; Receptor, Endothelin B; Receptors, Endothelin; SOXE Transcription Factors; Snail Family Transcription Factors; Transcription Factors; Waardenburg Syndrome
PubMed: 24379252
DOI: 10.5604/17322693.1077722 -
Microsurgery Jan 2014The biology behind vascularized bone allotransplantation remains largely unknown. We aim to study cell traffic between donor and recipient following bone auto-, and...
BACKGROUND
The biology behind vascularized bone allotransplantation remains largely unknown. We aim to study cell traffic between donor and recipient following bone auto-, and allografting.
METHODS
Vascularized femoral transplantation was performed with arteriovenous bundle implantation and short-term immunosuppression. Twenty male Piebald Virol Glaxo (PVG; RT1(c) ) rats received isotransplants from female PVG (RT1(c) ) rats and 22 male PVG rats received allografts from female Dark Agouti rats (DA, RT1(a) ), representing a major histocompatibility mismatch. Both groups were randomly analyzed at 4 or 18 weeks. Bone remodeling areas (inner and outer cortical samples) were labeled and laser capture microdissected. Analysis of sex-mismatch genes by real-time reverse transcription-polymerase chain reaction provided the relative Expression Ratio (rER) of donor (female) to recipient (male) cells.
RESULTS
The rER was 0.456 ± 0.266 at 4 weeks and 0.749 ± 0.387 at 18 weeks (p = 0.09) in allotransplants. In isotransplants, the rER was 0.412 ± 0.239 and 0.467 ± 0.252 at 4 and 18 weeks, respectively (p = 0.21). At 4 weeks, the rER at the outer cortical area of isotransplants was significantly lower in isotransplants as compared with allotransplants (0.247 ± 0.181 vs. 0.549 ± 0.184, p = 0.007). Cells in the inner and outer cortical bone remodeling areas in isotransplants were mainly donor derived (rER < 0.5) at 18 weeks, whereas allotransplants contained mainly recipient-derived cells (rER > 0.5) at 18 weeks.
CONCLUSIONS
Applying novel methodology, we describe detailed cell traffic in vascularized bone transplants, elaborating our comprehension on bone transplantation.
Topics: Animals; Bone Transplantation; Bone and Bones; Cell Lineage; Female; Male; Rats; Transplantation, Homologous
PubMed: 24038399
DOI: 10.1002/micr.22147 -
BioMed Research International 2013Piebaldism is a rare autosomal dominant disorder of melanocyte development, which is mostly caused by KIT gene. The key characteristics of piebaldism include localized...
Piebaldism is a rare autosomal dominant disorder of melanocyte development, which is mostly caused by KIT gene. The key characteristics of piebaldism include localized poliosis, congenital leukoderma, and other variable manifestations. The previous study has illustrated that the homogeneous MC1R (a gene which is associated with the hair color) variant (p.I120T) coordinating with KIT mutation may lead to auburn hair color and piebaldism. In this study, we have investigated a Chinese family with piebaldism and auburn hair color; the mutation screening of KIT and MC1R genes identified that only a splicing mutation (c. 2484+1G>A) of KIT gene cosegregated with the auburn hair color and piebaldism. The data of this study and others suggests that the KIT mutation may causes of the auburn hair color in the piebaldism patients.
Topics: Adult; Alternative Splicing; Child; China; Female; Hair Color; Humans; Male; Mutation; Pedigree; Piebaldism; Proto-Oncogene Proteins c-kit
PubMed: 24000325
DOI: 10.1155/2013/689756 -
Annales de Biologie Clinique 2013Griscelli syndrome type 2 is a rare autosomal recessive disorder, due to a mutation in RAB27A gene. It associates partial albinism, silver hair and immune deficiency. We...
Griscelli syndrome type 2 is a rare autosomal recessive disorder, due to a mutation in RAB27A gene. It associates partial albinism, silver hair and immune deficiency. We report the case of a 6 year-old boy who was admitted to the Emergency department with severe sepsis complicated by hemophagocytic syndrome. Many clinical and biological criteria leads to the diagnosis of type 2 Griscelli syndrome: consanguineous family, recurrent infection, absence of psychomotor retardation, oculocutaneous albinism, silver hair, occurrence of hemophagocytic syndrome and especially the pathognomonic appearance on microscopic examination of the hair. The absence of giant organelles inclusion in all granulated cells eliminated Chediak-Higashi syndrome.
Topics: Chediak-Higashi Syndrome; Child; Diagnosis, Differential; Fatal Outcome; Hair; Humans; Immunologic Deficiency Syndromes; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation; Male; Organelles; Piebaldism; Pigments, Biological; Primary Immunodeficiency Diseases; Sepsis
PubMed: 23906575
DOI: 10.1684/abc.2013.0860 -
Experimental Cell Research Sep 2013A fully functional immune system is essential to protect the body against pathogens and other diseases, including cancer. Vesicular trafficking provides the correct... (Review)
Review
A fully functional immune system is essential to protect the body against pathogens and other diseases, including cancer. Vesicular trafficking provides the correct localization of proteins within all cell types, but this process is most exquisitely controlled and coordinated in immune cells because of their specialized organelles and their requirement to respond to selected stimuli. More than 60 Rab GTPases play important roles in protein trafficking, but only five Rab-encoding genes have been associated with inherited human disorders, and only one of these (Rab27a) causes an immune defect. Mutations in RAB27A cause Griscelli Syndrome type 2 (GS2), an autosomal recessive disorder of pigmentation and severe immune deficiency. In lymphocytes, Munc13-4 is an effector of Rab27a, and mutations in the gene encoding this protein (UNC13D) cause Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL3). The immunological features of GS2 and FHL3 include neutropenia, thrombocytopenia, and immunodeficiency due to impaired function of cytotoxic lymphocytes. The small number of disorders caused by mutations in genes encoding Rabs could be due to their essential functions, where defects in these genes could be lethal. However, with the increasing use of next generation sequencing technologies, more mutations in genes encoding Rabs may be identified in the near future.
Topics: Chediak-Higashi Syndrome; Crohn Disease; Gene Expression Regulation; Hermanski-Pudlak Syndrome; Humans; Immunologic Deficiency Syndromes; Lymphohistiocytosis, Hemophagocytic; Membrane Proteins; Mutation; Piebaldism; Primary Immunodeficiency Diseases; Protein Transport; Signal Transduction; T-Lymphocytes, Cytotoxic; Transport Vesicles; rab GTP-Binding Proteins; rab27 GTP-Binding Proteins
PubMed: 23810987
DOI: 10.1016/j.yexcr.2013.06.012 -
Brazilian Journal of Biology = Revista... Feb 2013Anomalous colourations occur in many tropical vertebrates. However, they are considered rare in wild populations, with very few records for the majority of animal taxa.... (Review)
Review
Anomalous colourations occur in many tropical vertebrates. However, they are considered rare in wild populations, with very few records for the majority of animal taxa. We report two new cases of anomalous colouration in mammals. Additionally, we compiled all published cases about anomalous pigmentation registered in Neotropical mammals, throughout a comprehensive review of peer reviewed articles between 1950 and 2010. Every record was classified as albinism, leucism, piebaldism or eventually as undetermined pigmentation. As results, we report the new record of a leucistic specimen of opossum (Didelphis sp.) in southern Brazil, as well as a specimen of South American fur seal (Arctocephalus australis) with piebaldism in Uruguay. We also found 31 scientific articles resulting in 23 records of albinism, 12 of leucism, 71 of piebaldism and 92 records classified as undetermined pigmentation. Anomalous colouration is apparently rare in small terrestrial mammals, but it is much more common in cetaceans and michrochiropterans. Out of these 198 records, 149 occurred in cetaceans and 30 in bats. The results related to cetaceans suggest that males and females with anomolous pigmentation are reproductively successful and as a consequence their frequencies are becoming higher in natural populations. In bats, this result can be related to the fact these animals orient themselves primarily through echolocation, and their refuges provide protection against light and predation. It is possible that anomalous colouration occurs more frequently in other Neotropical mammal orders, which were not formally reported. Therefore, we encourage researchers to publish these events in order to better understand this phenomenon that has a significant influence on animal survival.
Topics: Albinism; Animals; Didelphis; Female; Fur Seals; Humans; Male; Piebaldism; Pigmentation Disorders
PubMed: 23644801
DOI: 10.1590/s1519-69842013000100020