Abstract
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.
MeSH terms
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Animals
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Animals, Newborn
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Chloride Channels
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Female
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Gene Dosage
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Kidney Tubules, Distal / cytology
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Kidney Tubules, Distal / embryology*
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Kidney Tubules, Distal / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Knockout
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Mucoproteins / genetics
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Mucoproteins / metabolism
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Nerve Tissue Proteins
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Neuropeptides / genetics
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Neuropeptides / metabolism*
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POU Domain Factors
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Potassium Channels / genetics
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Potassium Channels / metabolism
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Potassium Channels, Inwardly Rectifying*
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Pregnancy
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Receptors, Prostaglandin E / genetics
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Receptors, Prostaglandin E / metabolism
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Receptors, Prostaglandin E, EP3 Subtype
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Renal Insufficiency
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Sodium-Potassium-Chloride Symporters / genetics
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Sodium-Potassium-Chloride Symporters / metabolism
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Solute Carrier Family 12, Member 1
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Uromodulin
Substances
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Bsnd protein, mouse
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Chloride Channels
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Kcnj1 protein, mouse
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Membrane Proteins
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Mucoproteins
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Nerve Tissue Proteins
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Neuropeptides
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POU Domain Factors
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Ptger3 protein, mouse
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Receptors, Prostaglandin E
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Receptors, Prostaglandin E, EP3 Subtype
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Slc12a1 protein, mouse
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Sodium-Potassium-Chloride Symporters
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Solute Carrier Family 12, Member 1
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Trans-Activators
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Umod protein, mouse
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Uromodulin
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Pou3f3 protein, mouse