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Cleft Palate, Moderate Lung Developmental Retardation and Early Postnatal Lethality in Mice Deficient in the Kir7.1 Inwardly Rectifying K+ Channel.

Villanueva S, Burgos J, López-Cayuqueo KI, Lai KM, Valenzuela DM, Cid LP, Sepúlveda FV - PLoS ONE (2015)

Bottom Line: Kir7.1 is present in epithelial tissues where it colocalizes with the Na+/K+-pump probably serving to recycle K+ taken up by the pump.Kir7.1 is expressed in the epithelium covering the palatal processes at the time at which palate sealing takes place and our results suggest it might play an essential role in late palatogenesis.Our work also reveals a second unexpected role in the development and the physiology of the respiratory system, where Kir7.1 is expressed in epithelial cells all along the respiratory tree.

View Article: PubMed Central - PubMed

Affiliation: Centro de Estudios Científicos (CECs), Valdivia, Chile.

ABSTRACT
Kir7.1 is an inwardly rectifying K+ channel of the Kir superfamily encoded by the kcnj13 gene. Kir7.1 is present in epithelial tissues where it colocalizes with the Na+/K+-pump probably serving to recycle K+ taken up by the pump. Human mutations affecting Kir7.1 are associated with retinal degeneration diseases. We generated a mouse lacking Kir7.1 by ablation of the Kcnj13 gene. Homozygous mutant mice die hours after birth and show cleft palate and moderate retardation in lung development. Kir7.1 is expressed in the epithelium covering the palatal processes at the time at which palate sealing takes place and our results suggest it might play an essential role in late palatogenesis. Our work also reveals a second unexpected role in the development and the physiology of the respiratory system, where Kir7.1 is expressed in epithelial cells all along the respiratory tree.

No MeSH data available.


Related in: MedlinePlus

Sites of Kir7.1 channel expression in the respiratory system.a. Tissue cryostat sections (10μm) from trachea, bronchiole, terminal bronchiole and alveoli) of two month old Kcnj13+/- (top) and Kcnj13+/+ (bottom) mice were stained with X-Gal (blue) and counterstained with eosin. b. Kir7.1 channel expression during respiratory system development. Tissue cryostat sections were stained with X-Gal and counterstained with eosin. The embryonic age is indicated. c. Higher magnification views of tissues at embryonic stages E17.5 and E18.5. Bars represent 100 μm.
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pone.0139284.g002: Sites of Kir7.1 channel expression in the respiratory system.a. Tissue cryostat sections (10μm) from trachea, bronchiole, terminal bronchiole and alveoli) of two month old Kcnj13+/- (top) and Kcnj13+/+ (bottom) mice were stained with X-Gal (blue) and counterstained with eosin. b. Kir7.1 channel expression during respiratory system development. Tissue cryostat sections were stained with X-Gal and counterstained with eosin. The embryonic age is indicated. c. Higher magnification views of tissues at embryonic stages E17.5 and E18.5. Bars represent 100 μm.

Mentions: Respiratory distress consequent to delayed lung development is a frequent cause of perinatal mortality. There are no reports of Kir7.1 expression in the respiratory system of the mouse or any other species. We have used the expression of the bacterial β-galactosidase (LacZ) reporter that is driven by the Kcjn13 promoter in tissues from Kcjn13+/- and Kcjn13-/- mice to check for expression in the channel in the respiratory system. Kir7.1 was expressed in mouse airways and lungs as seen from the presence of LacZ activity (Fig 2a) in the epithelium of the trachea, bronchioles and terminal bronchioles as well as in the alveoli of Kcjn13+/- mice. In this last location the stain appeared to associate with type II pneumocytes (not shown). Analysis of embryonic tissue (Fig 2b and 2c) revealed that LacZ, and therefore Kir7.1 channel expression was absent at 15.5 dpc but emerged at 16.5 dpc and was present at delivery. Higher magnification showing the epithelial expression of Kir7.1 is presented in Fig 2c. The presence of Kir7.1 protein in the respiratory system was corroborated by immunolocalization. The immunolabel was present in trachea, bronchi and lung tissue of P0 and adult mouse, in the first two tissues at the basolateral aspect of epithelia cells (Fig 3).


Cleft Palate, Moderate Lung Developmental Retardation and Early Postnatal Lethality in Mice Deficient in the Kir7.1 Inwardly Rectifying K+ Channel.

Villanueva S, Burgos J, López-Cayuqueo KI, Lai KM, Valenzuela DM, Cid LP, Sepúlveda FV - PLoS ONE (2015)

Sites of Kir7.1 channel expression in the respiratory system.a. Tissue cryostat sections (10μm) from trachea, bronchiole, terminal bronchiole and alveoli) of two month old Kcnj13+/- (top) and Kcnj13+/+ (bottom) mice were stained with X-Gal (blue) and counterstained with eosin. b. Kir7.1 channel expression during respiratory system development. Tissue cryostat sections were stained with X-Gal and counterstained with eosin. The embryonic age is indicated. c. Higher magnification views of tissues at embryonic stages E17.5 and E18.5. Bars represent 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4581704&req=5

pone.0139284.g002: Sites of Kir7.1 channel expression in the respiratory system.a. Tissue cryostat sections (10μm) from trachea, bronchiole, terminal bronchiole and alveoli) of two month old Kcnj13+/- (top) and Kcnj13+/+ (bottom) mice were stained with X-Gal (blue) and counterstained with eosin. b. Kir7.1 channel expression during respiratory system development. Tissue cryostat sections were stained with X-Gal and counterstained with eosin. The embryonic age is indicated. c. Higher magnification views of tissues at embryonic stages E17.5 and E18.5. Bars represent 100 μm.
Mentions: Respiratory distress consequent to delayed lung development is a frequent cause of perinatal mortality. There are no reports of Kir7.1 expression in the respiratory system of the mouse or any other species. We have used the expression of the bacterial β-galactosidase (LacZ) reporter that is driven by the Kcjn13 promoter in tissues from Kcjn13+/- and Kcjn13-/- mice to check for expression in the channel in the respiratory system. Kir7.1 was expressed in mouse airways and lungs as seen from the presence of LacZ activity (Fig 2a) in the epithelium of the trachea, bronchioles and terminal bronchioles as well as in the alveoli of Kcjn13+/- mice. In this last location the stain appeared to associate with type II pneumocytes (not shown). Analysis of embryonic tissue (Fig 2b and 2c) revealed that LacZ, and therefore Kir7.1 channel expression was absent at 15.5 dpc but emerged at 16.5 dpc and was present at delivery. Higher magnification showing the epithelial expression of Kir7.1 is presented in Fig 2c. The presence of Kir7.1 protein in the respiratory system was corroborated by immunolocalization. The immunolabel was present in trachea, bronchi and lung tissue of P0 and adult mouse, in the first two tissues at the basolateral aspect of epithelia cells (Fig 3).

Bottom Line: Kir7.1 is present in epithelial tissues where it colocalizes with the Na+/K+-pump probably serving to recycle K+ taken up by the pump.Kir7.1 is expressed in the epithelium covering the palatal processes at the time at which palate sealing takes place and our results suggest it might play an essential role in late palatogenesis.Our work also reveals a second unexpected role in the development and the physiology of the respiratory system, where Kir7.1 is expressed in epithelial cells all along the respiratory tree.

View Article: PubMed Central - PubMed

Affiliation: Centro de Estudios Científicos (CECs), Valdivia, Chile.

ABSTRACT
Kir7.1 is an inwardly rectifying K+ channel of the Kir superfamily encoded by the kcnj13 gene. Kir7.1 is present in epithelial tissues where it colocalizes with the Na+/K+-pump probably serving to recycle K+ taken up by the pump. Human mutations affecting Kir7.1 are associated with retinal degeneration diseases. We generated a mouse lacking Kir7.1 by ablation of the Kcnj13 gene. Homozygous mutant mice die hours after birth and show cleft palate and moderate retardation in lung development. Kir7.1 is expressed in the epithelium covering the palatal processes at the time at which palate sealing takes place and our results suggest it might play an essential role in late palatogenesis. Our work also reveals a second unexpected role in the development and the physiology of the respiratory system, where Kir7.1 is expressed in epithelial cells all along the respiratory tree.

No MeSH data available.


Related in: MedlinePlus