Assuntos
Queratina-16/genética , Ceratodermia Palmar e Plantar Difusa/genética , Mutação , Papiloma/genética , Animais , Modelos Animais de Doenças , Cães , Éxons , Feminino , Humanos , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Masculino , Microscopia de Fluorescência , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Especificidade da EspécieRESUMO
Metastatic calcinosis associated with chronic renal failure and multiple urinary tract abnormalities was diagnosed in a 6-month-old Brittany spaniel that was presented with calcinosis cutis. This case report highlights the importance of skin as an indicator of systemic disease. The aetiopathogenesis of the four main types of tissue calcification is defined and discussed with an emphasis on metastatic calcinosis.
Assuntos
Calcinose/veterinária , Doenças do Cão/diagnóstico , Dermatopatias/veterinária , Sistema Urinário/anormalidades , Animais , Calcinose/diagnóstico , Calcinose/etiologia , Doenças do Cão/etiologia , Cães , Feminino , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/veterinária , Dermatopatias/diagnóstico , Dermatopatias/etiologiaRESUMO
Junctional epidermolysis bullosa (JEB) is a genodermatosis suitable for gene therapy because conventional treatments are ineffective. Here, we elucidate the genetic basis of mild JEB in a breed of dogs that display all the clinical traits observed in JEB patients. The condition is associated with reduced expression of laminin 5 caused by a homozygous insertion (4818+207ins6.5 kb) of repetitive satellite DNA within intron 35 of the gene (lama3) for the laminin alpha3 chain. The intronic mutation interferes with maturation of the alpha3 pre-messenger RNA resulting in the coexpression of a transcript with a 227 nucleotide insertion and a wild-type mRNA that encodes scant amounts of the alpha3 polypeptide. Our results show that the amino acid sequence and structure of the canine and human alpha3 chain are highly conserved and that the reduced expression of laminin 5 affects the adhesion and clonogenic potential of the JEB keratinocytes. These JEB dogs provide the opportunity to perform gene delivery in a naturally occurring genodermatosis and to evaluate host tolerance to recombinant laminin 5.