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1.
Br J Dermatol ; 161(2): 265-72, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19438474

RESUMEN

BACKGROUND: Congenital, nonepidermolytic cornification disorders phenotypically resembling human autosomal recessive ichthyosis have been described in purebred dog breeds, including Jack Russell terrier (JRT) dogs. One cause of gene mutation important to humans and dogs is transposon insertions. OBJECTIVES: To describe an autosomal recessive, severe nonepidermolytic ichthyosis resembling lamellar ichthyosis (LI) in JRT dogs due to insertion of a long interspersed nucleotide element (LINE-1) in the transglutaminase 1 (TGM1) gene. METHODS: Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Phenotypic information and genotyping with a canine microsatellite marker suggested TGM1 to be a candidate gene. Genomic DNA samples and cDNA generated from epidermal RNA were examined. Consequences of the mutation were evaluated by Western blotting, quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme activity from cultured keratinocytes. RESULTS: Affected dogs had generalized severe hyperkeratosis. Histological examination defined laminated to compact hyperkeratosis without epidermolysis; ultrastructurally, cornified envelopes were thin. Affected dogs were homozygous for a 1980-bp insertion within intron 9 of TGM1. The sequence of the insertion was that of a canine LINE-1 element. Quantitative RT-PCR indicated a significant decrease in TGM1 mRNA in affected dogs compared with wild-type. TGM1 protein was markedly decreased on immunoblotting, and membrane-associated enzyme activity was diminished in affected dogs. CONCLUSIONS: Based on morphological and molecular features, this disease is homologous with TGM1-deficient LI in humans, clinically models LI better than the genetically modified mouse and represents its first spontaneous animal model. This is the first reported form of LI due to transposon insertion.


Asunto(s)
Enfermedades de los Perros/genética , Ictiosis Lamelar/veterinaria , Elementos de Nucleótido Esparcido Largo/genética , Mutagénesis Insercional/genética , Transglutaminasas/genética , Animales , Biopsia/veterinaria , Elementos Transponibles de ADN/genética , Enfermedades de los Perros/patología , Perros , Femenino , Marcadores Genéticos , Ictiosis Lamelar/genética , Ictiosis Lamelar/patología , Inmunohistoquímica , Intrones/genética , Masculino , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Piel/patología , Especificidad de la Especie , Transglutaminasas/deficiencia , Transglutaminasas/metabolismo
2.
Br J Dermatol ; 153(1): 51-8, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16029326

RESUMEN

BACKGROUND: Epidermolytic hyperkeratosis in humans is caused by dominant-negative mutations in suprabasal epidermal keratins 1 and 10. However, spontaneous keratin mutations have not been confirmed in a species other than human. OBJECTIVES: To describe an autosomal recessive, mild, nonpalmar/plantar epidermolytic ichthyosis segregating in an extended pedigree of Norfolk terrier dogs due to a splice-site mutation in the gene encoding keratin 10 (KRT10). METHODS: Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Genomic DNA samples and cDNA from skin RNA were sequenced and defined a mutation in KRT10. Consequences of the mutation were evaluated by assessing protein expression with immunohistochemistry and Western blotting and gene expression with real-time RT-PCR (reverse transcriptase-polymerase chain reaction). RESULTS: Adult dogs with the disease had generalized, pigmented hyperkeratosis with epidermal fragility. Light microscopic examination defined epidermolysis with hyperkeratosis; ultrastructural changes included a decrease in tonofilaments and abnormal filament aggregation in upper spinous and granular layer keratinocytes. Affected dogs were homozygous for a single base GT-->TT change in the consensus donor splice site of intron 5 in KRT10. Keratin 10 protein was not detected with immunoblotting in affected dogs. Heterozygous dogs were normal based on clinical and histological appearance and keratin 10 protein expression. The mutation caused activation of at least three cryptic or alternative splice sites. Use of the cryptic sites resulted in transcripts containing premature termination codons. One transcript could result in shortening of the proximal portion of the 2B domain before the stutter region. Quantitative real-time PCR indicated a significant decrease in KRT10 mRNA levels in affected dogs compared with wild-type dogs. CONCLUSIONS: This disease is the first confirmed spontaneous keratin mutation in a nonhuman species and is the first reported recessive form of epidermolytic hyperkeratosis.


Asunto(s)
Enfermedades de los Perros/genética , Hiperqueratosis Epidermolítica/veterinaria , Queratinas/genética , Mutación Puntual , Animales , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/patología , Perros , Femenino , Expresión Génica , Genes Recesivos , Hiperqueratosis Epidermolítica/genética , Hiperqueratosis Epidermolítica/metabolismo , Hiperqueratosis Epidermolítica/patología , Queratina-10 , Queratinas/metabolismo , Masculino , Linaje , Sitios de Empalme de ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Piel/metabolismo
3.
J Speech Hear Res ; 33(2): 375-9, 1990 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-2359277

RESUMEN

This research note presents the results of a content analysis of the Columbia Mental Maturity Scale and the Test of Nonverbal Intelligence (TONI). We also compared the intratest performance of a selected sample of language-impaired (LI) and MA-matched normal language children on these two tests. These analyses are an extension of Johnston's (1982) report on the Leiter. The content analysis revealed differences in the nature of perceptual and conceptual items on the Columbia and the TONI. Consistent with Johnston's findings, the intratest comparisons revealed no significant group differences. LI and normal-language children performed significantly better on the perceptual-type items than the conceptual-type items. The predominance of perceptual items was particularly evident in the TONI.


Asunto(s)
Pruebas de Inteligencia/normas , Trastornos del Desarrollo del Lenguaje/fisiopatología , Comunicación no Verbal , Preescolar , Cognición , Estudios de Evaluación como Asunto , Humanos , Inteligencia , Pruebas de Inteligencia/instrumentación , Trastornos del Desarrollo del Lenguaje/diagnóstico , Memoria , Percepción , Reproducibilidad de los Resultados , Pensamiento
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