RESUMO
PURPOSE: To investigate the morphology and function of photoreceptors in mice with mutation of the FSCN2 gene. METHODS: A mouse line was generated carrying the 208delG mutation (point mutation, or p-type) and another with replacement of exon 1 by the cDNA of a green fluorescent protein (GFP knock-in, or g-type). The expression of retinal mRNA was determined by reverse transcription (RT)-polymerase chain reaction (PCR) and in situ hybridization performed on retinal sections. Morphologic analyses of the retinas were performed by light microscopy (LM) and transmission electron microscopy (TEM) and functional analyses by electroretinogram (ERG). RESULTS: mRNA of FSCN2 was not detected in the retinal mRNA extracted from FSCN2p/p and FSCN2g/g mice. Both FSCN2(+/p) and FSCN2(+/g) mice had progressive photoreceptor degeneration with increasing age detected by LM and structural abnormalities of the outer segment (OS) detected by TEM. Both FSCN2(+/p) and FSCN2(+/g) mice had depressed rod and cone ERGs that worsened with increasing age. CONCLUSIONS: These results indicate that haploinsufficiency of the FSCN2 gene may hamper maintenance and/or elongation of the OS disks and result in photoreceptor degeneration, as in human autosomal dominant retinitis pigmentosa.
Assuntos
Proteínas de Transporte/genética , Deleção de Genes , Proteínas dos Microfilamentos/deficiência , Proteínas dos Microfilamentos/genética , Células Fotorreceptoras de Vertebrados/ultraestrutura , Mutação Puntual , Retinose Pigmentar/genética , Animais , Eletrorretinografia , Feminino , Marcação de Genes , Genes Dominantes , Proteínas de Fluorescência Verde/genética , Hibridização In Situ , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/metabolismo , Retinose Pigmentar/metabolismo , Retinose Pigmentar/patologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
This study identifies a role for the gene for the POU transcription factor Brn1 in distal tubule formation and function in the mammalian kidney. Normal development of Henle's loop (HL), the distal convoluted tubule and the macula densa was severely retarded in Brn1-deficient mice. In particular, elongation and differentiation of the developing HL was affected. In the adult kidney, Brn1 was detected only in the thick ascending limb (TAL) of HL. In addition, the expression of a number of TAL-specific genes was reduced in the Brn1+/- kidney, including Umod, Nkcc2/Slc12a1, Bsnd, Kcnj1 and Ptger3. These results suggest that Brn1 is essential for both the development and function of the nephron in the kidney.
Assuntos
Túbulos Renais Distais/embriologia , Túbulos Renais Distais/metabolismo , Neuropeptídeos/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização , Transativadores/metabolismo , Animais , Animais Recém-Nascidos , Canais de Cloreto , Feminino , Dosagem de Genes , Túbulos Renais Distais/citologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Mucoproteínas/genética , Mucoproteínas/metabolismo , Proteínas do Tecido Nervoso , Neuropeptídeos/genética , Fatores do Domínio POU , Canais de Potássio/genética , Canais de Potássio/metabolismo , Gravidez , Receptores de Prostaglandina E/genética , Receptores de Prostaglandina E/metabolismo , Receptores de Prostaglandina E Subtipo EP3 , Insuficiência Renal , Simportadores de Cloreto de Sódio-Potássio/genética , Simportadores de Cloreto de Sódio-Potássio/metabolismo , Membro 1 da Família 12 de Carreador de Soluto , Transativadores/genética , UromodulinaRESUMO
Formation of highly organized neocortical structure depends on the production and correct placement of the appropriate number and types of neurons. POU homeodomain proteins Brn-1 and Brn-2 are coexpressed in the developing neocortex, both in the late precursor cells and in the migrating neurons. Here we show that double disruption of both Brn-1 and Brn-2 genes in mice leads to abnormal formation of the neocortex with dramatically reduced production of layer IV-II neurons and defective migration of neurons unable to express mDab1. These data indicate that Brn-1 and Brn-2 share roles in the production and positioning of neocortical neuron development.