Limits...
Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice.

Miyamoto T, Morita K, Takemoto D, Takeuchi K, Kitano Y, Miyakawa T, Nakayama K, Okamura Y, Sasaki H, Miyachi Y, Furuse M, Tsukita S - J. Cell Biol. (2005)

Bottom Line: Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits.Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons.These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Graduate School of Medicine, Kyoto University, Japan.

ABSTRACT
Tight junction (TJ)-like structures have been reported in Schwann cells, but their molecular composition and physiological function remain elusive. We found that claudin-19, a novel member of the claudin family (TJ adhesion molecules in epithelia), constituted these structures. Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits. Electrophysiological analyses showed that the claudin-19 deficiency affected the nerve conduction of peripheral myelinated fibers. Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons. These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.

Show MeSH

Related in: MedlinePlus

Behavioral abnormalities in claudin-19–deficient mice. All behavioral tests were performed with male Cld19+/+ and Cld19−/− mice that were ∼10–13–wk old at the start of the testing. Details of each test were described in Materials and methods. In the beam test, both on thick and thin bars, Cld19−/− mice exhibited significantly more frequent slips than Cld19+/+ mice (P < 0.0001). In the rotarod test, Cld19−/− mice dropped from the rotating rod more quickly than Cld19+/+ mice (P = 0.0002). In these tests, especially in the rotarod test, the performance of both Cld19+/+ and Cld19−/− mice improved as the trials were repeated, suggesting that the neuronal deficits of Cld19−/− mice observed in these tests were not attributed to the defects in the CNS but to those in the PNS. Consistent with this, in the open field test, the total distance traveled during 30 min was not significantly different between Cld19+/+ and Cld19−/− mice. Vertical activity and time spent in the center or the beam-break count for stereotyped behavior were not affected by the claudin-19 deficiency (not depicted). Finally, the prepulse inhibition test was performed to examine the extent to which the startle response of mice to the stimulus sound (110 or 120 dB) was inhibited by the prepulse stimulus sound (74 or 78 dB). The startle amplitude itself was not different between Cld19+/+ and Cld19−/− mice, and the inhibition by prepulse stimuli was not significantly affected in Cld19−/− mice. The data obtained from the open field test and prepulse inhibition test again suggested that Cld19−/− mice suffered from a kind of peripheral neuropathy.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2171943&req=5

fig4: Behavioral abnormalities in claudin-19–deficient mice. All behavioral tests were performed with male Cld19+/+ and Cld19−/− mice that were ∼10–13–wk old at the start of the testing. Details of each test were described in Materials and methods. In the beam test, both on thick and thin bars, Cld19−/− mice exhibited significantly more frequent slips than Cld19+/+ mice (P < 0.0001). In the rotarod test, Cld19−/− mice dropped from the rotating rod more quickly than Cld19+/+ mice (P = 0.0002). In these tests, especially in the rotarod test, the performance of both Cld19+/+ and Cld19−/− mice improved as the trials were repeated, suggesting that the neuronal deficits of Cld19−/− mice observed in these tests were not attributed to the defects in the CNS but to those in the PNS. Consistent with this, in the open field test, the total distance traveled during 30 min was not significantly different between Cld19+/+ and Cld19−/− mice. Vertical activity and time spent in the center or the beam-break count for stereotyped behavior were not affected by the claudin-19 deficiency (not depicted). Finally, the prepulse inhibition test was performed to examine the extent to which the startle response of mice to the stimulus sound (110 or 120 dB) was inhibited by the prepulse stimulus sound (74 or 78 dB). The startle amplitude itself was not different between Cld19+/+ and Cld19−/− mice, and the inhibition by prepulse stimuli was not significantly affected in Cld19−/− mice. The data obtained from the open field test and prepulse inhibition test again suggested that Cld19−/− mice suffered from a kind of peripheral neuropathy.

Mentions: Cld19−/− mice appeared to walk awkwardly on a smooth surface, especially on a smooth rod. Therefore, we subjected these mice (∼10–13–wk-old male Cld19+/+ and Cld19−/− mice) to several established behavioral tests (Fig. 4). First, a “beam test” was performed, in which we counted how many times a hindlimb slips while a mouse is walking a given distance on a thin or thick bar. Interestingly, Cld19−/− mice exhibited significantly more slips on these bars than Cld19+/+ mice. Second, these mice were subjected to a “rotarod test.” In this test, mice were put on a rotating rod, and how long they remained on the rod was measured. Cld19−/− mice fell from the rod more quickly than Cld19+/+ mice. Importantly, in both tests, but especially in the rotarod test, Cld19−/− mice performed better as the trials were repeated (similar to Cld19+/+ mice), which was consistent with the notion that the neuronal deficits of Cld19−/− mice observed in these tests were attributable to defects in the PNS. Furthermore, to evaluate CNS functions in Cld19−/− mice, we performed two more behavior tests, the “open field test” and the “prepulse inhibition test” (see Materials and methods). In these tests, no behavioral abnormalities were detected in Cld19−/− mice. Thus, taking the PNS-specific expression of claudin-19 in the nervous system into consideration, we concluded that Cld19−/− mice suffered from a kind of peripheral neuropathy.


Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice.

Miyamoto T, Morita K, Takemoto D, Takeuchi K, Kitano Y, Miyakawa T, Nakayama K, Okamura Y, Sasaki H, Miyachi Y, Furuse M, Tsukita S - J. Cell Biol. (2005)

Behavioral abnormalities in claudin-19–deficient mice. All behavioral tests were performed with male Cld19+/+ and Cld19−/− mice that were ∼10–13–wk old at the start of the testing. Details of each test were described in Materials and methods. In the beam test, both on thick and thin bars, Cld19−/− mice exhibited significantly more frequent slips than Cld19+/+ mice (P < 0.0001). In the rotarod test, Cld19−/− mice dropped from the rotating rod more quickly than Cld19+/+ mice (P = 0.0002). In these tests, especially in the rotarod test, the performance of both Cld19+/+ and Cld19−/− mice improved as the trials were repeated, suggesting that the neuronal deficits of Cld19−/− mice observed in these tests were not attributed to the defects in the CNS but to those in the PNS. Consistent with this, in the open field test, the total distance traveled during 30 min was not significantly different between Cld19+/+ and Cld19−/− mice. Vertical activity and time spent in the center or the beam-break count for stereotyped behavior were not affected by the claudin-19 deficiency (not depicted). Finally, the prepulse inhibition test was performed to examine the extent to which the startle response of mice to the stimulus sound (110 or 120 dB) was inhibited by the prepulse stimulus sound (74 or 78 dB). The startle amplitude itself was not different between Cld19+/+ and Cld19−/− mice, and the inhibition by prepulse stimuli was not significantly affected in Cld19−/− mice. The data obtained from the open field test and prepulse inhibition test again suggested that Cld19−/− mice suffered from a kind of peripheral neuropathy.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171943&req=5

fig4: Behavioral abnormalities in claudin-19–deficient mice. All behavioral tests were performed with male Cld19+/+ and Cld19−/− mice that were ∼10–13–wk old at the start of the testing. Details of each test were described in Materials and methods. In the beam test, both on thick and thin bars, Cld19−/− mice exhibited significantly more frequent slips than Cld19+/+ mice (P < 0.0001). In the rotarod test, Cld19−/− mice dropped from the rotating rod more quickly than Cld19+/+ mice (P = 0.0002). In these tests, especially in the rotarod test, the performance of both Cld19+/+ and Cld19−/− mice improved as the trials were repeated, suggesting that the neuronal deficits of Cld19−/− mice observed in these tests were not attributed to the defects in the CNS but to those in the PNS. Consistent with this, in the open field test, the total distance traveled during 30 min was not significantly different between Cld19+/+ and Cld19−/− mice. Vertical activity and time spent in the center or the beam-break count for stereotyped behavior were not affected by the claudin-19 deficiency (not depicted). Finally, the prepulse inhibition test was performed to examine the extent to which the startle response of mice to the stimulus sound (110 or 120 dB) was inhibited by the prepulse stimulus sound (74 or 78 dB). The startle amplitude itself was not different between Cld19+/+ and Cld19−/− mice, and the inhibition by prepulse stimuli was not significantly affected in Cld19−/− mice. The data obtained from the open field test and prepulse inhibition test again suggested that Cld19−/− mice suffered from a kind of peripheral neuropathy.
Mentions: Cld19−/− mice appeared to walk awkwardly on a smooth surface, especially on a smooth rod. Therefore, we subjected these mice (∼10–13–wk-old male Cld19+/+ and Cld19−/− mice) to several established behavioral tests (Fig. 4). First, a “beam test” was performed, in which we counted how many times a hindlimb slips while a mouse is walking a given distance on a thin or thick bar. Interestingly, Cld19−/− mice exhibited significantly more slips on these bars than Cld19+/+ mice. Second, these mice were subjected to a “rotarod test.” In this test, mice were put on a rotating rod, and how long they remained on the rod was measured. Cld19−/− mice fell from the rod more quickly than Cld19+/+ mice. Importantly, in both tests, but especially in the rotarod test, Cld19−/− mice performed better as the trials were repeated (similar to Cld19+/+ mice), which was consistent with the notion that the neuronal deficits of Cld19−/− mice observed in these tests were attributable to defects in the PNS. Furthermore, to evaluate CNS functions in Cld19−/− mice, we performed two more behavior tests, the “open field test” and the “prepulse inhibition test” (see Materials and methods). In these tests, no behavioral abnormalities were detected in Cld19−/− mice. Thus, taking the PNS-specific expression of claudin-19 in the nervous system into consideration, we concluded that Cld19−/− mice suffered from a kind of peripheral neuropathy.

Bottom Line: Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits.Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons.These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Graduate School of Medicine, Kyoto University, Japan.

ABSTRACT
Tight junction (TJ)-like structures have been reported in Schwann cells, but their molecular composition and physiological function remain elusive. We found that claudin-19, a novel member of the claudin family (TJ adhesion molecules in epithelia), constituted these structures. Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits. Electrophysiological analyses showed that the claudin-19 deficiency affected the nerve conduction of peripheral myelinated fibers. Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons. These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.

Show MeSH
Related in: MedlinePlus