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1.
Mamm Genome ; 34(3): 449-452, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36867211

RESUMO

The 35th International Mammalian Genome Conference (IMGC) was held on July 17-20, 2022 in Vancouver, British Columbia; this conference marked the first time the International Mammalian Genome Society (IMGS) hosted a meeting in Canada. Scientists from around the world participated to share advances in genetics and genomics research across mammalian species. A diverse attendance of pre-doctoral and post-doctoral trainees, young investigators, established researchers, clinicians, bioinformaticians, and computational biologists enjoyed a rich scientific program selected from 88 abstracts in the fields of cancer, conservation genetics, developmental biology, epigenetics, human disease modeling, immunology, infectious diseases, systems genetics, translational biology, and technological advances.


Assuntos
Genoma , Genômica , Animais , Humanos , Proteômica , Epigenômica , Epigênese Genética , Mamíferos/genética
2.
Hum Mol Genet ; 29(R1): R107-R116, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32592473

RESUMO

Temple syndrome (TS) and Kagami-Ogata syndrome (KOS) are imprinting disorders caused by absence or overexpression of genes within a single imprinted cluster on human chromosome 14q32. TS most frequently arises from maternal UPD14 or epimutations/deletions on the paternal chromosome, whereas KOS most frequently arises from paternal UPD14 or epimutations/deletions on the maternal chromosome. In this review, we describe the clinical symptoms and genetic/epigenetic features of this imprinted region. The locus encompasses paternally expressed protein-coding genes (DLK1, RTL1 and DIO3) and maternally expressed lncRNAs (MEG3/GTL2, RTL1as and MEG8), as well as numerous miRNAs and snoRNAs. Control of expression is complex, with three differentially methylated regions regulating germline, placental and tissue-specific transcription. The strong conserved synteny between mouse chromosome 12aF1 and human chromosome 14q32 has enabled the use of mouse models to elucidate imprinting mechanisms and decipher the contribution of genes to the symptoms of TS and KOS. In this review, we describe relevant mouse models and highlight their value to better inform treatment options for long-term management of TS and KOS patients.


Assuntos
Anormalidades Múltiplas , Transtornos Cromossômicos/patologia , Cromossomos Humanos Par 14/genética , Modelos Animais de Doenças , Impressão Genômica , Hallux/anormalidades , Deficiência Intelectual/patologia , Unhas Malformadas/patologia , Polegar/anormalidades , Dissomia Uniparental/patologia , Animais , Transtornos Cromossômicos/genética , Hallux/patologia , Humanos , Deficiência Intelectual/genética , Camundongos , Unhas Malformadas/genética , Fenótipo , Polegar/patologia , Dissomia Uniparental/genética
3.
Mamm Genome ; 32(5): 319-322, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34091719

RESUMO

The 34th International Mammalian Genome Conference (IMGC) was held in conjunction with The Allied Genetics Conference (TAGC2020). Scientists from more than 30 countries participated in TAGC2020 to share advances in genetics and genomics research across species. The mammalian section, represented mostly by International Mammalian Genome Society (IMGS) members, had 239 in-person registrants and the number of registrants grew to 3520 virtual attendees when the meeting was converted from an in-person format to a virtual format. A diverse attendance of pre-doctoral and post-doctoral trainees, young investigators, established researchers, clinicians, bioinformaticians, and computational biologists enjoyed a rich scientific program selected from 184 submitted (Mammalian) abstracts in the fields of epigenetics, system genetics, developmental biology, cancer, human disease modeling, technical advances, and bioinformatics.


Assuntos
Genoma , Mamíferos/genética , Animais
5.
Proc Natl Acad Sci U S A ; 109(18): E1082-91, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22451924

RESUMO

To address the role of Tpl2, a MAP3K8 that regulates innate/adaptive immunity and inflammation, in intestinal tumorigenesis, we crossed a Tpl2 KO allele into the Apc(min/+) genetic background. Here, we show that Apc(min/+)/Tpl2(-/-) mice exhibit a fivefold increase in the number of intestinal adenomas. Bone marrow transplantation experiments revealed that the enhancement of polyposis was partially hematopoietic cell-driven. Consistent with this observation, Tpl2 ablation promoted intestinal inflammation. IL-10 levels and regulatory T-cell numbers were lower in the intestines of Tpl2(-/-) mice, independent of Apc and polyp status, suggesting that they were responsible for the initiation of the enhancement of tumorigenesis caused by the ablation of Tpl2. The low IL-10 levels correlated with defects in mTOR activation and Stat3 phosphorylation in Toll-like receptor-stimulated macrophages and with a defect in inducible regulatory T-cell generation and function. Both polyp numbers and inflammation increased progressively with time. The rate of increase of both, however, was more rapid in Apc(min/+)/Tpl2(-/-) mice, suggesting that the positive feedback initiated by inflammatory signals originating in developing polyps is more robust in these mice. This may be because these mice have a higher intestinal polyp burden as a result of the enhancement of tumor initiation.


Assuntos
Genes APC , Doenças Inflamatórias Intestinais/etiologia , Interleucina-10/biossíntese , Neoplasias Intestinais/etiologia , MAP Quinase Quinase Quinases/deficiência , Proteínas Proto-Oncogênicas/deficiência , Linfócitos T Reguladores/imunologia , Adenoma/etiologia , Adenoma/genética , Adenoma/imunologia , Animais , Transplante de Medula Óssea , Feminino , Expressão Gênica , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Mucosa Intestinal/imunologia , Neoplasias Intestinais/genética , Neoplasias Intestinais/imunologia , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Modelos Imunológicos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/imunologia
6.
PLoS Genet ; 12(9): e1006299, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27657702
7.
Nat Genet ; 37(11): 1210-2, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16200063

RESUMO

Stratifin (Sfn, also called 14-3-3sigma) is highly expressed in differentiating epidermis and mediates cell cycle arrest. Sfn is repressed in cancer, but its function during development is uncharacterized. We identified an insertion mutation in the gene Sfn in repeated epilation (Er) mutant mice by positional cloning. Er/+ mice expressed a truncated Sfn protein, which probably contributes to the defects in Er/Er and Er/+ epidermis and to cancer development in Er/+ mice.


Assuntos
Alopecia/genética , Biomarcadores Tumorais/genética , Exonucleases/genética , Remoção de Cabelo , Camundongos Mutantes/anatomia & histologia , Mutação/genética , Proteínas de Neoplasias/genética , Neoplasias Cutâneas/genética , Proteínas 14-3-3 , Alopecia/patologia , Animais , Células Epidérmicas , Exorribonucleases , Heterozigoto , Masculino , Camundongos , Dados de Sequência Molecular , Fenótipo
8.
Sci Rep ; 13(1): 393, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624251

RESUMO

Salmonella enterica serovar Typhi is the causative agent of typhoid fever restricted to humans and does not replicate in commonly used inbred mice. Genetic variation in humans is far greater and more complex than that in a single inbred strain of mice. The Collaborative Cross (CC) is a large panel of recombinant inbred strains which has a wider range of genetic diversity than laboratory inbred mouse strains. We found that the CC003/Unc and CC053/Unc strains are permissive to intraperitoneal but not oral route of S. Typhi infection and show histopathological changes characteristic of human typhoid. These CC strains are immunocompetent, and immunization induces antigen-specific responses that can kill S. Typhi in vitro and control S. Typhi in vivo. Our results indicate that CC003/Unc and CC053/Unc strains can help identify the genetic basis for typhoid susceptibility, S. Typhi virulence mechanism(s) in vivo, and serve as a preclinical mammalian model system to identify effective vaccines and therapeutics strategies.


Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas , Animais , Humanos , Camundongos , Salmonella typhi , Camundongos de Cruzamento Colaborativo , Mamíferos
9.
Carcinogenesis ; 33(8): 1589-97, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22637734

RESUMO

Every year thousands of people in the USA are diagnosed with small intestine and colorectal cancers (CRC). Although environmental factors affect disease etiology, uncovering underlying genetic factors is imperative for risk assessment and developing preventative therapies. Familial adenomatous polyposis is a heritable genetic disorder in which individuals carry germ-line mutations in the adenomatous polyposis coli (APC) gene that predisposes them to CRC. The Apc ( Min ) mouse model carries a point mutation in the Apc gene and develops polyps along the intestinal tract. Inbred strain background influences polyp phenotypes in Apc ( Min ) mice. Several Modifier of Min (Mom) loci that alter tumor phenotypes associated with the Apc ( Min ) mutation have been identified to date. We screened BXH recombinant inbred (RI) strains by crossing BXH RI females with C57BL/6J (B6) Apc ( Min ) males and quantitating tumor phenotypes in backcross progeny. We found that the BXH14 RI strain harbors five modifier loci that decrease polyp multiplicity. Furthermore, we show that resistance is determined by varying combinations of these modifier loci. Gene interaction network analysis shows that there are multiple networks with proven gene-gene interactions, which contain genes from all five modifier loci. We discuss the implications of this result for studies that define susceptibility loci, namely that multiple networks may be acting concurrently to alter tumor phenotypes. Thus, the significance of this work resides not only with the modifier loci we identified but also with the combinations of loci needed to get maximal protection against polyposis and the impact of this finding on human disease studies.


Assuntos
Genes APC , Animais , Colo/patologia , Feminino , Mutação em Linhagem Germinativa , Pólipos Intestinais/genética , Intestino Delgado/patologia , Masculino , Camundongos , Camundongos Endogâmicos
10.
Med Sci Educ ; 32(2): 305-308, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35433108

RESUMO

In April and May 2020, a group of students and professors from the Hackensack Meridian School of Medicine (HMSOM) created an elective to review pre-selected, de-identified COVID-19-related research proposals by physicians and researchers within the Hackensack Meridian Health (HMH) network. Students discussed and rated each proposal's significance, innovation, and approach using grading criteria that paralleled the National Institute of Health's (NIH) study section-based grant review process. In discussing these topics under the guidance of faculty with experience in writing and reviewing research grants, students gained a better understanding of what constitutes a quality research study and a compelling grant proposal.

12.
Mamm Genome ; 21(9-10): 450-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20886217

RESUMO

The adenomatous polyposis coli (APC) gene is known to act as a tumor suppressor gene in both sporadic and hereditary colorectal cancer by negatively regulating WNT signaling. Familial adenomatous polyposis (FAP) patients develop intestinal polyps due to the presence of a single germline mutation in APC. The severity of the FAP phenotype is a function of the position of the APC mutation, indicating a complex role for APC that extends beyond the canonical WNT pathway. APC encodes a large protein with multiple functional domains, including an armadillo repeat domain that has been linked to protein-protein interactions. To determine the effect of the armadillo repeat domain on intestinal tumorigenesis, we generated a congenic mouse line (Apc ( Δ242 )) carrying a gene trap cassette between exons 7 and 8 of the murine Apc gene. Apc ( Δ242/+) mice express a truncated Apc product lacking the armadillo repeat domain as part of a fusion protein with ß-geo. Expression of the fusion product was confirmed by X-gal staining, ensuring that Apc ( Δ242 ) is not a null allele. In contrast, Apc ( Min/+) mice produce a truncated Apc product that contains an intact armadillo repeat domain. On the C57BL/6J background, Apc ( Δ242/+) mice develop more polyps than do Apc ( Min/+) mice along the entire length of the small intestine; however, polyps were significantly smaller in Apc ( Δ242/+) mice. In addition, polyp multiplicity in Apc ( Δ242/+) mice is affected by polymorphisms between inbred strains. These data suggest that the armadillo repeat domain of the Apc protein suppresses tumor initiation in the murine intestine while also promoting tumor growth.


Assuntos
Proteína da Polipose Adenomatosa do Colo/química , Polipose Adenomatosa do Colo , Genes APC , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/metabolismo , Polipose Adenomatosa do Colo/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Alelos , Sequência de Aminoácidos , Animais , Proteínas do Domínio Armadillo/química , Proteínas do Domínio Armadillo/genética , Proteínas do Domínio Armadillo/metabolismo , Modelos Animais de Doenças , Fusão Gênica , Pólipos Intestinais/genética , Pólipos Intestinais/metabolismo , Pólipos Intestinais/patologia , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , Estrutura Terciária de Proteína , Deleção de Sequência , Transdução de Sinais , beta-Galactosidase/genética
13.
Mol Carcinog ; 48(9): 821-31, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19263440

RESUMO

Apc mutations cause intestinal tumorigenesis through Tcf4 activation. However, direct techniques for studying Tcf4 activation in vivo are limited. Here, we describe the development of a Tcf4-GFP reporter mouse model for directly studying Tcf4 activation. We first developed a GFP reporter construct (Tcf4-GFP) and transfected it into SW480 cells that have constitutively activated Tcf4. Reporter activity increased 47-fold. Next, we created transgenic (Tg) mice by transducing the construct into C57BL/6J mice. Fluorescence microscopy did not detect GFP in intestinal sections, but flow cytometry showed 5% of crypt cells to be GFP(+). We then established cross-bred mice (Tg x Apc(Min/+)), which have a germline Apc mutation and sustained Tcf4 activation. Here, fluorescence microscopy showed GFP(+) cells at or near the base of normal-appearing crypts. In adenomas, in which Apc is inactivated, GFP(+) signal was even greater. Immunostaining for the Tcf4 target genes survivin (BIRC5) and cyclin D1 (CCND1) showed that their expression also paralleled GFP positivity. We conclude that GFP directly reports Tcf4 activation in vivo and tracks the predicted increases in Tcf4 activation that result from Apc inactivation, and that Apc mutation contributes to survivin and cyclin D1 overexpression through Tcf4 activation. Our Tcf4 mouse should be useful in studying the effects of chemopreventive agents on Wnt signaling and changes in proliferative crypt cell populations-including stem cells-during intestinal tumorigenesis.


Assuntos
Proteína da Polipose Adenomatosa do Colo/fisiologia , Neoplasias Intestinais/patologia , Mutação , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição TCF/metabolismo , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Enterócitos/metabolismo , Enterócitos/patologia , Feminino , Citometria de Fluxo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose , Neoplasias Intestinais/genética , Neoplasias Intestinais/metabolismo , Antígeno Ki-67/metabolismo , Luciferases/genética , Luciferases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras , Survivina , Fatores de Transcrição TCF/genética , Fator de Transcrição 4
14.
J Invest Dermatol ; 138(11): 2470-2479, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29753032

RESUMO

In addition to playing a role in adhesion, desmoglein 2 (Dsg2) is an important regulator of growth and survival signaling pathways, cell proliferation, migration and invasion, and oncogenesis. Although low-level Dsg2 expression is observed in basal keratinocytes and is downregulated in nonhealing venous ulcers, overexpression has been observed in both melanomas and nonmelanoma malignancies. Here, we show that transgenic mice overexpressing Dsg2 in basal keratinocytes primed the activation of mitogenic pathways, but did not induce dramatic epidermal changes or susceptibility to chemical-induced tumor development. Interestingly, acceleration of full-thickness wound closure and increased wound-adjacent keratinocyte proliferation was observed in these mice. As epidermal cytokines and their receptors play critical roles in wound healing, Dsg2-induced secretome alterations were assessed with an antibody profiler array and revealed increased release and proteolytic processing of the urokinase-type plasminogen activator receptor. Dsg2 induced urokinase-type plasminogen activator receptor expression in the skin of transgenic compared with wild-type mice. Wounding further enhanced urokinase-type plasminogen activator receptor in both epidermis and dermis with a concomitant increase in the prohealing laminin-332, a major component of the basement membrane zone, in transgenic mice. This study demonstrates that Dsg2 induces epidermal activation of various signaling cascades and accelerates cutaneous wound healing, in part, through urokinase-type plasminogen activator receptor-related signaling cascades.


Assuntos
Desmogleína 2/metabolismo , Queratinócitos/fisiologia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Pele/patologia , Cicatrização/genética , Animais , Moléculas de Adesão Celular/metabolismo , Proliferação de Células , Células Cultivadas , Desmogleína 2/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais , Pele/metabolismo , Calinina
15.
Cancer Res ; 77(22): 6051-6059, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-29097610

RESUMO

Alterations in mitochondrial DNA (mtDNA) were once thought to be predominantly innocuous to cell growth. Recent evidence suggests that mtDNA undergo naturally occurring alterations, including mutations and polymorphisms, which profoundly affect the cells in which they appear and contribute to a variety of diseases, including cardiovascular disease, diabetes, and cancer. Furthermore, interplay between mtDNA and nuclear DNA has been found in cancer cells, necessitating consideration of these complex interactions for future studies of cancer mutations and polymorphisms. In this issue of Cancer Research, Vivian and colleagues utilize a unique mouse model, called Mitochondrial Nuclear eXchange mice, that contain the nuclear DNA from one inbred mouse strain, and the mtDNA from a different inbred mouse strain to examine the genome-wide nuclear DNA methylation and gene expression patterns of brain tissue. Results demonstrated there were alterations in nuclear DNA expression and DNA methylation driven by mtDNA. These alterations may impact disease pathogenesis. In light of these results, in this review, we highlight alterations in mtDNA, with a specific focus on polymorphisms associated with cancer susceptibility and/or prognosis, mtDNA as cancer biomarkers, and considerations for investigating the role of mtDNA in cancer progression for future studies. Cancer Res; 77(22); 6051-9. ©2017 AACR.


Assuntos
DNA Mitocondrial/genética , Proteínas Mitocondriais/genética , Neoplasias/genética , Polimorfismo Genético , Animais , Biomarcadores Tumorais/genética , Predisposição Genética para Doença/genética , Humanos , Camundongos , Mutação , Neoplasias/patologia
16.
Oncogene ; 24(42): 6450-8, 2005 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-16007193

RESUMO

The secreted phospholipase A2 type IIA (Pla2g2a) gene was previously identified as a modifier of intestinal adenoma multiplicity in Apc Min/+ mice. To determine if intestinal secreted phospholipase A2 (sPLA2) activity was also attenuated in susceptible strains, we developed a sensitive assay to directly quantitate sPLA2 activity in the murine intestinal tract utilizing a fluorescent BODIPY-labeled phospholipid substrate. Here, we report assay conditions that distinguish between secreted and cytosolic PLA2 enzyme activities in extracts of intestinal tissue. The small intestine exhibited higher activity levels than the large intestine. Consistent with predictions from the sPLA2-IIA gene sequence in inbred strains, we detected low levels of enzyme activity in inbred strains containing sPLA2-IIA mutations; these strains were also associated with greater numbers of intestinal polyps. Additionally, the assay was able to distinguish differences in levels of sPLA2 activity between neoplasia-resistant strains, which were then shown by sequencing to carry variant wild-type sPLA2-IIA alleles. Immunohistochemical analyses of intestinal tissues were consistent with sPLA2-IIA activity levels. This approach enables further studies of the mechanisms of sPLA2 action influencing the development and tumorigenesis of the small intestine and colon in both mice and humans.


Assuntos
Transformação Celular Neoplásica/genética , Genes APC , Fosfolipases A/metabolismo , Sequência de Aminoácidos , Animais , Compostos de Boro , Fosfolipases A2 do Grupo II , Imuno-Histoquímica , Neoplasias Intestinais/enzimologia , Intestino Grosso/enzimologia , Intestino Delgado/enzimologia , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Peso Molecular , Fosfolipases A/química , Fosfolipases A/genética , Fosfolipases A2 , Homologia de Sequência de Aminoácidos , Especificidade da Espécie
17.
Cancer Res ; 62(19): 5413-7, 2002 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-12359746

RESUMO

Intestinal adenoma development in Apc(Min) mice is influenced by genetic background. We generated a congenic line between the CAST and B6 inbred strains to study the effects of a resistant CAST background in the absence of a major modifier locus, Modifier of Min 1 (Mom1(R)). Progeny from a CAST.B6 Mom1(R/S) x B6 Apc(Min/+) intercross were 110 or 200 days of age and screened for intestinal polyps. There was a significant decrease (P < 0.0001) in polyp multiplicity and size in CASTB6F1 Mom1(R/S), Apc(Min/+) and CASTB6F1 Mom1(S/S), Apc(Min/+) progeny compared with B6 Mom1(S/S), Apc(Min/+) controls. A complete absence of colon polyps was observed in all mice heterozygous for the CAST background. These results demonstrate that the CAST strain carries dominant modifier loci, in addition to Mom1(R), that dramatically reduce polyp burden in the small intestine and eliminate polyp burden in the colon of Apc(Min) mice.


Assuntos
Polipose Adenomatosa do Colo/genética , Genes APC/fisiologia , Camundongos Endogâmicos/genética , Alelos , Animais , Cruzamentos Genéticos , Feminino , Predisposição Genética para Doença/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
J Invest Dermatol ; 123(6): 1052-6, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15610513

RESUMO

Collagen, the major macromolecular component of skin, is responsible for maintaining the structural integrity of the tissue as well as for providing important functional characteristics, such as pliability and thickness. We have been studying the structure and regulation of collagen in mouse mutations affecting the skin. In the course of these studies, we found that there are significant differences in collagen content between the skin of wild-type male and female mice, which become evident at puberty. Furthermore, male mice with an X-linked mutation in the androgen receptor gene (formerly called testicular feminization and abbreviated as Ar(Tfm)) showed decreased levels of collagen, indicating that the androgen receptor pathway contributes to the observed differences. These findings demonstrate that there are striking differences in the collagen content of skin between male and female mice, and provide a biochemical explanation for these differences.


Assuntos
Síndrome de Resistência a Andrógenos/fisiopatologia , Colágeno/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Pele/metabolismo , Síndrome de Resistência a Andrógenos/metabolismo , Síndrome de Resistência a Andrógenos/patologia , Animais , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Rim/metabolismo , Rim/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Fatores Sexuais , Pele/patologia
19.
Biochem Res Int ; 2013: 436053, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24260716

RESUMO

The Tight Skin mouse is a genetically induced animal model of tissue fibrosis caused by a large in-frame mutation in the gene encoding fibrillin-1 (Fbn-1). We examined the influence of gender on the collagen content of tissues in C57BL/6J wild type (+/+) and mutant Tight Skin (Tsk/+) mice employing hydroxyproline assays. Tissue sections were stained with Masson's trichrome to identify collagen in situ. Adult Tsk/+ mice skin contains ~15% more collagen, on average, than skin from +/+ mice of the same gender. The heart of Tsk/+ males had significantly more collagen than that of +/+ males. No significant gender differences were found in lungs and kidney collagen content. Overall, the collagen content of Tsk/+ males and +/+ males was higher than that of their Tsk/+ and +/+ female counterparts, respectively. Our data confirm increased deposition of collagen in skin and hearts of Tsk/+ mice; however, the effects of the Tsk mutation on collagen content are both tissue specific and gender specific. These results indicate that comparative studies of collagen content between normal and Tsk/+ mice skin and internal organs must take into account gender differences caused by expression of the androgen receptor.

20.
Dis Model Mech ; 4(3): 305-10, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21558063

RESUMO

The mouse is the leading organism for disease research. A rich resource of genetic variation occurs naturally in inbred and special strains owing to spontaneous mutations. However, one can also obtain desired gene mutations by using the following processes: targeted mutations that eliminate function in the whole organism or in a specific tissue; forward genetic screens using chemicals or transposons; or the introduction of exogenous transgenes as DNAs, bacterial artificial chromosomes (BACs) or reporter constructs. The mouse is the only mammal that provides such a rich resource of genetic diversity coupled with the potential for extensive genome manipulation, and is therefore a powerful application for modeling human disease. This poster review outlines the major genome manipulations available in the mouse that are used to understand human disease: natural variation, reverse genetics, forward genetics, transgenics and transposons. Each of these applications will be essential for understanding the diversity that is being discovered within the human population.


Assuntos
Modelos Animais de Doenças , Doença/genética , Animais , Elementos de DNA Transponíveis/genética , Variação Genética , Genética , Humanos , Camundongos , Camundongos Transgênicos
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