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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

Pulmonary abnormalities in embryonic lungs from Kcnj13-/- mice.a. Hematoxylin and eosin stained lung sections taken at various gestational stages as indicated. Morphological differences in KO lungs were observed at E18.5 and P0. Null mutant mice show a lower air space and thicker walls at lung terminal sacs compared to WT and heterozygous mice. No differences were visible between Kcnj13+/+ and Kcnj13+/- genotypes. Scale bars represent 100 μm. b. Morphometric analysis of terminal sac spaces in lungs at various gestational stages. Significant reduction in spaces was observed in Kir7.1 deficient mice from E18.5 onwards. Results are expressed as mean ± S.E.M, # p<0.05 and * p<0.01 for the difference with WT by ANOVA. c. Graphical representation of newborn lung flotation test. Grey sections of columns correspond to percent of floating lungs, with black being the percent sinking lungs.
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pone.0139284.g004: Pulmonary abnormalities in embryonic lungs from Kcnj13-/- mice.a. Hematoxylin and eosin stained lung sections taken at various gestational stages as indicated. Morphological differences in KO lungs were observed at E18.5 and P0. Null mutant mice show a lower air space and thicker walls at lung terminal sacs compared to WT and heterozygous mice. No differences were visible between Kcnj13+/+ and Kcnj13+/- genotypes. Scale bars represent 100 μm. b. Morphometric analysis of terminal sac spaces in lungs at various gestational stages. Significant reduction in spaces was observed in Kir7.1 deficient mice from E18.5 onwards. Results are expressed as mean ± S.E.M, # p<0.05 and * p<0.01 for the difference with WT by ANOVA. c. Graphical representation of newborn lung flotation test. Grey sections of columns correspond to percent of floating lungs, with black being the percent sinking lungs.

Mentions: Does the absence of Kir7.1 channel from mutant mice have any effect in lung development? This was examined histologically as seen in Fig 4a, that shows tissues from mice of the three genotypes in embryos from 15.5 to 18.5 dpc. No major differences between genotypes can be seen up to 17.5 dpc. At E18.5 and P0, when embryonic mouse lung develops from canalicular stage to saccular stage, there appears that spaces in the Kcjn13-/- tissue are smaller than in the WT or heterozygous tissue. This impression is borne out by the quantification of terminal sac spaces shown in Fig 4b. There was no difference between genotypes at 17.5 dpc, but terminal sacs of Kir7.1 deficient mice were significantly smaller than those in WT at 18.5 dpc, and that those of WT and heterozygous mice at P0. Failure to inflate lungs is not an uncommon consequence of lung immaturity and is encountered in several knockout mouse models [20]. Kcjn13-/- mice survived for up to 12 h after birth and did not appear cyanotic, suggesting an absence of respiratory distress. This is consistent with similar levels of expression of proSp-C (surfactant protein C) in lungs of Kcnj13+/+ and Kcnj13-/- P0 mice (not shown). Lungs dissected from Kcjn13+/+, Kcjn13+/- and Kcjn13-/- P0 mice floated when placed in saline solution suggesting that normal respiration had taken place (Fig 4c). Although some sinking lungs cropped up in the mutant and heterozygous mouse groups this tendency did not reach statistical significance.


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)

Pulmonary abnormalities in embryonic lungs from Kcnj13-/- mice.a. Hematoxylin and eosin stained lung sections taken at various gestational stages as indicated. Morphological differences in KO lungs were observed at E18.5 and P0. Null mutant mice show a lower air space and thicker walls at lung terminal sacs compared to WT and heterozygous mice. No differences were visible between Kcnj13+/+ and Kcnj13+/- genotypes. Scale bars represent 100 μm. b. Morphometric analysis of terminal sac spaces in lungs at various gestational stages. Significant reduction in spaces was observed in Kir7.1 deficient mice from E18.5 onwards. Results are expressed as mean ± S.E.M, # p<0.05 and * p<0.01 for the difference with WT by ANOVA. c. Graphical representation of newborn lung flotation test. Grey sections of columns correspond to percent of floating lungs, with black being the percent sinking lungs.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139284.g004: Pulmonary abnormalities in embryonic lungs from Kcnj13-/- mice.a. Hematoxylin and eosin stained lung sections taken at various gestational stages as indicated. Morphological differences in KO lungs were observed at E18.5 and P0. Null mutant mice show a lower air space and thicker walls at lung terminal sacs compared to WT and heterozygous mice. No differences were visible between Kcnj13+/+ and Kcnj13+/- genotypes. Scale bars represent 100 μm. b. Morphometric analysis of terminal sac spaces in lungs at various gestational stages. Significant reduction in spaces was observed in Kir7.1 deficient mice from E18.5 onwards. Results are expressed as mean ± S.E.M, # p<0.05 and * p<0.01 for the difference with WT by ANOVA. c. Graphical representation of newborn lung flotation test. Grey sections of columns correspond to percent of floating lungs, with black being the percent sinking lungs.
Mentions: Does the absence of Kir7.1 channel from mutant mice have any effect in lung development? This was examined histologically as seen in Fig 4a, that shows tissues from mice of the three genotypes in embryos from 15.5 to 18.5 dpc. No major differences between genotypes can be seen up to 17.5 dpc. At E18.5 and P0, when embryonic mouse lung develops from canalicular stage to saccular stage, there appears that spaces in the Kcjn13-/- tissue are smaller than in the WT or heterozygous tissue. This impression is borne out by the quantification of terminal sac spaces shown in Fig 4b. There was no difference between genotypes at 17.5 dpc, but terminal sacs of Kir7.1 deficient mice were significantly smaller than those in WT at 18.5 dpc, and that those of WT and heterozygous mice at P0. Failure to inflate lungs is not an uncommon consequence of lung immaturity and is encountered in several knockout mouse models [20]. Kcjn13-/- mice survived for up to 12 h after birth and did not appear cyanotic, suggesting an absence of respiratory distress. This is consistent with similar levels of expression of proSp-C (surfactant protein C) in lungs of Kcnj13+/+ and Kcnj13-/- P0 mice (not shown). Lungs dissected from Kcjn13+/+, Kcjn13+/- and Kcjn13-/- P0 mice floated when placed in saline solution suggesting that normal respiration had taken place (Fig 4c). Although some sinking lungs cropped up in the mutant and heterozygous mouse groups this tendency did not reach statistical significance.

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