Expression of the Na+–K+–2Cl− cotransporter in the rat endolymphatic sac

Akiyama, Kosuke; Miyashita, Takenori; Mori, Terushige; Mori, Nozomu

doi:10.1016/j.bbrc.2007.10.107

Cited by 25 publications

(20 citation statements)

References 29 publications

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“…The T4 antibody shows basolateral expression of NKCC1 protein in marginal cells of the stria vascularis, vestibular dark cells and neurons of the spiral and vestibular ganglia in the adult mouse (Delpire et al, 1999;Dixon et al, 1999), guinea pig (Jin et al, 2008) and gerbil (Crouch et al, 1997;Sakaguchi et al, 1998); protein expression is also seen in the endolymphatic sac of the rat (Akiyama et al, 2007). In the zebrafish ear, Nkcc1 protein expression is restricted to cells in the dorsolateral septum and the ventral semicircular canal pillar facing the utriculosaccular chamber.…”

Section: Nkcc1 Protein Expression In the Zebrafish Ear Is Tightly Regmentioning

confidence: 99%

Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva

Abbas

Whitfield

2009

Development

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Endolymph is the specialised extracellular fluid present inside the inner ear. In mammals, disruptions to endolymph homeostasis can result in either collapse or distension of the endolymphatic compartment in the cochlea, with concomitant hearing loss. The zebrafish little ears (lte) mutant shows a collapse of the otic vesicle in the larva, apparently owing to a loss of endolymphatic fluid in the ear, together with an over-inflation of the swim bladder. Mutant larvae display signs of abnormal vestibular function by circling and swimming upside down. The two available alleles of lte are homozygous lethal: mutant larvae fail to thrive beyond 6 days postfertilisation. Patterning of the otic vesicle is apparently normal. However, the expression of several genes thought to play a role in endolymph production is downregulated, including the sodium-potassium-chloride cotransporter gene nkcc1 (slc12a2) and several Na + /K + -ATPase channel subunit genes. We show here that lte mutations correspond to lesions in nkcc1. Each allele has a point mutation that disrupts splicing, leading to frame shifts in the coding region that predict the generation of truncated products. Endolymph collapse in the lte/nkcc1 mutant shows distinct parallels to that seen in mouse Nkcc1 mutants, validating zebrafish as a model for the study of endolymph disorders. The collapse in ear volume can be ameliorated in the to27d allele of lte by injection of a morpholino that blocks splicing at an ectopic site introduced by the mutation. This exemplifies the use of morpholinos as potential therapeutic agents for genetic disease.

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Section: Nkcc1 Protein Expression In the Zebrafish Ear Is Tightly Regmentioning

confidence: 99%

Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva

Abbas

Whitfield

2009

Development

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“…After aquaporin (AQP) water channels were discovered [1], it became clear that these channels play an important role in inner ear fluid homeostasis. In recent years, it has been reported that proteins and/ or mRNAs of AQP1 [2Á4], AQP2 [2,5], AQP3 [2,3], AQP4 [2,3], AQP5 [2], AQP6 [6], AQP7 [3], and AQP9 [3], vasopressin type 2 receptor (V 2 -R) [7], Na ' -K ' -Cl Á cotransporter (NKCC)1 [8,9], and NKCC2 [9] were expressed in the inner ear of experimental animals. It has also been reported that the AQP2 water regulation system is mediated by vasopressin (VP) [5,10], and many lines of evidence have led to the novel view that endolymphatic hydrops, which is a morphological characteristic of Meniere ' s disease, reflects malregulation of the VP-AQP2 system in inner ear fluid [10,11].…”

Section: Introductionmentioning

confidence: 99%

Expression of aquaporins, vasopressin type 2 receptor, and Na⁺-K⁺-Cl^–cotransporters in the rat endolymphatic sac

Nishimura

Kakigi

Takeda

et al. 2009

Acta Oto-Laryngologica

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“…This is partially due to the fact that expression of NKCC2 has been only recently found in extratubular cells. Indeed, NKCC2 is expressed in specialised neurons of the gastrointestinal tract or interneurons (Gavrikov et al 2006, Xue et al 2009, Zhu et al 2011 and in cells of the gastric, intestinal, endolymphatic sac and olfactory epithelia (Akiyama et al 2007, Nickell et al 2007, Nishimura et al 2009, Xue et al 2009, Zhu et al 2011. In fact, low levels of Slc12a1 mRNAs appear to be widely distributed in human tissues (Di Fulvio & Alvarez-Leefmans 2009).…”

Section: Introductionmentioning

confidence: 99%

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

Alshahrani

Fulvio

2012

Journal of Endocrinology

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The intracellular chloride concentration ([Cl co-transporters 2 and 1 respectively. We show that mice lacking functional alleles of the Slc12a2 gene exhibit better fasting glycaemia, increased insulin secretion in response to glucose, and improved glucose tolerance when compared with wildtype (WT). This phenomenon correlated with increased sensitivity of b-cells to glucose in vitro and with increased b-cell mass. Further, administration of low doses of BTD to mice deficient in Slc12a2 worsened their glucose tolerance, and low concentrations of BTD directly inhibited glucose-stimulated insulin secretion from b-cells deficient in Slc12a2 but expressing intact Slc12a1 genes. Together, our results suggest for the first time that the Slc12a2 gene is not necessary for insulin secretion and that its absence increases b-cell secretory capacity. Further, impairment of insulin secretion with BTD in vivo and in vitro in islets lacking Slc12a2 genes unmasks a potential new role for Slc12a1 in b-cell physiology.

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Expression of the Na+–K+–2Cl− cotransporter in the rat endolymphatic sac

Cited by 25 publications

References 29 publications

Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva

Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva

Expression of aquaporins, vasopressin type 2 receptor, and Na⁺-K⁺-Cl^–cotransporters in the rat endolymphatic sac

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

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Expression of the Na+–K+–2Cl− cotransporter in the rat endolymphatic sac

Cited by 25 publications

References 29 publications

Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva

Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva

Expression of aquaporins, vasopressin type 2 receptor, and Na+-K+-Cl–cotransporters in the rat endolymphatic sac

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

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Expression of aquaporins, vasopressin type 2 receptor, and Na⁺-K⁺-Cl^–cotransporters in the rat endolymphatic sac