Shintaro Inoue | GIFU Pharmaceutical University (original) (raw)
Papers by Shintaro Inoue
Vitiligo is a common but puzzling skin disorder characterized by the selective loss of epidermal ... more Vitiligo is a common but puzzling skin disorder characterized by the selective loss of epidermal melanocytes due to unknown mechanisms. Here, we show patients with vitiligo have disruptions of basement membrane zone (BMZ) architecture including branched, fragmented, and multilayered lamina densa with increased numbers of dermal fibroblasts and overexpression of MMP2 in those cells. Extracts of vitiliginous skin showed increased MMP2 protein expression, with a large portion of the MMP2 proteins in the active form. Intradermal injection of MMP2-overexpressing fibroblasts in K14-SCF transgenic mice induced a vitiligo-like skin appearance and disappearance of melanocytes, which were reversed by coadministration of MMP2 inhibitors. These results suggest that disorganization of the BMZ driven by MMP2 overexpression in dermal fibroblasts may cause the impaired melanocyte inhabitation observed in vitiligo.
Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique-... more Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique-hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsible for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and SC Cer, it is assumed that all major subfractions of SC Cer are generated from lamellar body-derived GlcCer. Yet, we and others have shown that SM-derived Cer are required for normal barrier homeostasis. Moreover, two pools of SM, one from plasma membrane, the other from lamellar body-derived contents, are potentially available for Cer production. To clarify the role of SM as a potential precursor of bulk or specific SC Cer, we compared Cer moieties in epidermal SM, Cer generated from epidermal SM by sphingomyelinase treatment, Cer within SC, and Cer that persist in Gaucher SC, where GlcCer cannot generate Cer due to an absence of -glucocerebrosidase. Using gas chromatographymass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance for Cer characterization, epidermal SM comprise three major subfractions with distinctive amide-linked (N-acyl) fatty acid (FA) compositions: that is, either long-chain FA (SM-1; C 22-26), short-chain FA (SM-2; primarily C 16), and short-chain ␣-hydroxy FA (SM-3; C 16-18). In contrast, only trace quantities of-hydroxy FA were present. For each SM subfraction, the sphingoid base was either sphingosine or sphinganine, but phytosphingosine was not detected. Comparison of these SM with corresponding sphingomyelinase-generated epidermal Cer and SC Cer revealed that the Cer moieties of SM-1 and SM-3 are equivalent to Cer 2 (NS) and Cer 5 (AS), respectively. Moreover, both Cer 2 and Cer 5 occurred in Gaucher SC, whereas other Cer subfractions did not occur. These results indicate that two epidermal SM, that is, SM-1 and SM-3, are important precursors of two corresponding Cer in mammalian SC, that is, Cer 2 and Cer 5, but other Cer species, including the-hydroxy Cer species, do not derive from SM.
Biochemical and Biophysical Research Communications, 2021
Gros et al., Alteration of tyrosinase activity in human . . . , Melanoma Research, vol. 4, pp. 35... more Gros et al., Alteration of tyrosinase activity in human . . . , Melanoma Research, vol. 4, pp. 359-364, 1994.* Ucar, Kalust, The effect of histamine ..., Biochem. Biophy. Res. Commun. vol. 199/1, pp. 545–550, 1991.* Tomita et al Histamine Stimulate normal human melanocytes in vitro ..., J. Dermatol. Sci. Vol. 6/2, pp. 146-154, 1993.* C.-Melanocyte Stimulating hormone and its analogue Nle"DPhe'o-MSH affect morphology, tyrosinase activity and melanogenesis in cultured human melanocytes, by Gil lian Hunt et al., Journal of Cell Science 107,205–211 (1994). Abstracts From the 9" Annual Meeting of the Japanese Society for Pigment Cell Research, Pigment Cell Research 1994; 7:365-374 (2 pages). Histamine Stimulates normal human melanocytes in vitro: one of the possible inducers of hyperpigmentation in urti caria pigmentosa, by Yasushi Tomita et al., Journal of Der matological Science 6 (1993) 146-154. Endothelin-1 as a New Melanogen: Coordinated Expression of Its Gene and the ...
International Journal of Neuropsychopharmacology, 2016
scores. A linear regression analysis revealed that being male and married had significant positiv... more scores. A linear regression analysis revealed that being male and married had significant positive associations with sexual arousal, sexual satisfaction, and/or sexual desire, while the presence of TD and a longer duration of illness were associated with poor sexual arousal and/or sexual desire. Additionally, sexual function was significantly associated with SWN-K and DAI scores in multivariate analysis. Conclusions: The acknowledgement and management of sexual dysfunction in patients with schizophrenia by clinicians may be important for improvement of their quality of life and adherence to medication.
Deep ocean water has long been known for its stable characteristics of rich mineral ingredients, ... more Deep ocean water has long been known for its stable characteristics of rich mineral ingredients, a low water temperature, and chemical and bacteriological purity, but the effects of deep ocean water on skin physiology remain obscure. In this study, we examined how cultured human skin keratinocytes responded to exposure to deep ocean water from the coastal waters of Toyama Prefecture. We found that these waters promoted not only keratinocyte proliferation, but also the formation of cornified envelope in the process of keratinocyte maturation (differentiation) into cornified cells. After reviewing the mineral ingredients in the seawater, we concluded that silicate promoted this envelope formation, and that coexisting calcium accelerated the effect of the silicate. As the homeostasis of skin depends heavily on a balanced skin turnover, with finely tuned coordination between proliferation and differentiation, this deep ocean water from Toyama is expected to be useful for skin care.
Proceedings for Annual Meeting of The Japanese Pharmacological Society
Journal of Investigative Dermatology, 1998
Journal of Dermatological Science
The Journal of Dermatology
A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderm... more A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol‐induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism‐based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol‐induced leukoderma helps not only elucidate the mechanisms of non‐segmental vitiligo onset and progression, but also suggests prevention and treatment.
Experimental Dermatology
Although atopic dermatitis (AD) has been reported to be a typical type 2 immune response disease,... more Although atopic dermatitis (AD) has been reported to be a typical type 2 immune response disease, it is also an inflammatory skin disease that involves cytokines, such as Th1, Th17, and Th22. However, little is known about the mechanism by which the candidate cytokines, alone or in combination, are involved in AD pathology. Differences in cytokine balance, which contribute to the complexity of AD pathology, may influence the stratum corneum barrier function through tight junction (TJ) functional stability and contribute to disease severity. To confirm the regulatory mechanism of TJ protein expression in AD, we investigated the Th1 and Th17 pathways, which are the initiation factors of chronic AD pathology. We examined the effects of these cytokines on TJ protein expression in normal human epidermal keratinocytes in vitro. We also examined their function in a human skin-equivalent model. We observed a time- and dose-dependent inhibitory effect of claudin-1 on IFN-γ via the IFN-γ receptor/JAK/STAT signaling pathway. IFN-γ impaired TJ function in a human skin-equivalent model. Moreover, we investigated co-stimulation with IL-17A, which is highly expressed in AD skin lesions, and found that IL-17A restores IFN-γ-induced TJ dysfunction. This restoration of TJ function was mediated by atypical protein kinase C zeta activation without recovery of TJ protein expression. These results are informative for personalized AD treatment via systemic therapies using anti-cytokine antibodies and/or JAK inhibitors.
International Journal of Molecular Sciences
Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein tha... more Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that plays an important role in cancer metastasis and osteoblast differentiation. In the skin epidermis, GPNMB is mainly expressed in melanocytes and plays a critical role in melanosome formation. In our previous study, GPNMB was also found to be expressed in skin epidermal keratinocytes. In addition, decreased GPNMB expression was observed in the epidermis of lesional skin of patients with vitiligo. However, the exact role of keratinocyte-derived GPNMB and its effect on vitiligo is still unknown. In this study, we demonstrated that GPNMB expression was also decreased in rhododendrol-induced leukoderma, as seen in vitiligo. The extracellular soluble form of GPNMB (sGPNMB) was found to protect melanocytes from cytotoxicity and the impairment of melanogenesis induced by oxidative stress. Furthermore, the effect of rGPNMB was not altered by the knockdown of CD44, which is a well-known receptor...
The Journal of Dermatology
Biochemical and biophysical research communications, Jan 20, 2018
We have previously reported that HYBID (hyaluronan (HA)-binding protein involved in HA depolymeri... more We have previously reported that HYBID (hyaluronan (HA)-binding protein involved in HA depolymerization/KIAA1199/CEMIP) is a specific HA-binding protein that is essential for HA depolymerization in skin and synovial fibroblasts. HA is incorporated into cells in the presence of HYBID and clathrin, degraded in endosomes, and excreted into the extracellular space. However, it is not yet clear whether HYBID itself catalytically cleaves HA. A recent report on transmembrane protein 2 (TMEM2)-a novel cell surface hyaluronidase-prompted us to investigate whether TMEM2 is essential for HYBID-mediated HA depolymerization. In the present study, we found that transforming growth factor beta 1 (TGF-β1), which suppressed HA depolymerization with a concomitant decrease in HYBID expression, upregulated TMEM2 expression conversely in human skin fibroblasts. TMEM2 expression was not affected by histamine, which significantly increased HA depolymerization accompanied by an increase in HYBID expression...
Biochemical and biophysical research communications, Jan 27, 2018
HYBID (hyaluronan binding protein involved in hyaluronan [HA] depolymerization, KIAA1199/CEMIP) i... more HYBID (hyaluronan binding protein involved in hyaluronan [HA] depolymerization, KIAA1199/CEMIP) is a key player in HA depolymerization of the skin fibroblasts, arthritic synovial fibroblasts, and brain. Our previous study demonstrated that Hybid knock-out (KO) mice showed spatial memorial impairment, which is accompanied by the accumulation of high molecular weight HA in the hippocampus. However, the mechanism underlying cognitive impairment by Hybid deficiency remains unclear. In the present study, we examined the HA distribution patterns in the brains of wild-type (WT) and Hybid KO mice by HA staining using HA binding protein, and found that in Hybid KO mice, HA is accumulated and doublecortin-positive immature neurons are significantly decreased in the dentate gyrus of the hippocampus, where Hybid mRNA is highly expressed in WT mice. The Golgi-Cox staining demonstrated that the dendritic spine density is significantly decreased in the dentate gyrus granule cells in Hybid KO mice....
Neuroscience, Apr 7, 2017
HYBID (HYaluronan Binding Protein Involved in hyaluronan [HA] Depolymerization, KIAA1199) is one ... more HYBID (HYaluronan Binding Protein Involved in hyaluronan [HA] Depolymerization, KIAA1199) is one of the HA binding proteins that is involved in the depolymerization of HA. HYBID mRNA is highly expressed in the brain, however, the role of HYBID in the brain remains unclear. In this study, we bred Hybid knock-out (KO) mice and evaluated the function of Hybid in the central nervous system. Hybid mRNA was expressed in the brain, especially in the hippocampus and cerebellum, in wild-type mice. Hybid KO mice demonstrated decreased mnemonic ability in novel object recognition and Morris water maze tests. The average molecular mass of hippocampal HA increased in KO mice, accompanied by a significant increase in the total HA amount. Hybid KO mice did not differ in behavior from wild-type mice in the open field test, evaluation of acoustic startle responses, or drug-induced seizure test. In real-time PCR, Hyal1 and Hyal2 mRNA levels, which code hyaluronidases 1 and 2, respectively, did not di...
Vitiligo is a common but puzzling skin disorder characterized by the selective loss of epidermal ... more Vitiligo is a common but puzzling skin disorder characterized by the selective loss of epidermal melanocytes due to unknown mechanisms. Here, we show patients with vitiligo have disruptions of basement membrane zone (BMZ) architecture including branched, fragmented, and multilayered lamina densa with increased numbers of dermal fibroblasts and overexpression of MMP2 in those cells. Extracts of vitiliginous skin showed increased MMP2 protein expression, with a large portion of the MMP2 proteins in the active form. Intradermal injection of MMP2-overexpressing fibroblasts in K14-SCF transgenic mice induced a vitiligo-like skin appearance and disappearance of melanocytes, which were reversed by coadministration of MMP2 inhibitors. These results suggest that disorganization of the BMZ driven by MMP2 overexpression in dermal fibroblasts may cause the impaired melanocyte inhabitation observed in vitiligo.
Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique-... more Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique-hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsible for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and SC Cer, it is assumed that all major subfractions of SC Cer are generated from lamellar body-derived GlcCer. Yet, we and others have shown that SM-derived Cer are required for normal barrier homeostasis. Moreover, two pools of SM, one from plasma membrane, the other from lamellar body-derived contents, are potentially available for Cer production. To clarify the role of SM as a potential precursor of bulk or specific SC Cer, we compared Cer moieties in epidermal SM, Cer generated from epidermal SM by sphingomyelinase treatment, Cer within SC, and Cer that persist in Gaucher SC, where GlcCer cannot generate Cer due to an absence of -glucocerebrosidase. Using gas chromatographymass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance for Cer characterization, epidermal SM comprise three major subfractions with distinctive amide-linked (N-acyl) fatty acid (FA) compositions: that is, either long-chain FA (SM-1; C 22-26), short-chain FA (SM-2; primarily C 16), and short-chain ␣-hydroxy FA (SM-3; C 16-18). In contrast, only trace quantities of-hydroxy FA were present. For each SM subfraction, the sphingoid base was either sphingosine or sphinganine, but phytosphingosine was not detected. Comparison of these SM with corresponding sphingomyelinase-generated epidermal Cer and SC Cer revealed that the Cer moieties of SM-1 and SM-3 are equivalent to Cer 2 (NS) and Cer 5 (AS), respectively. Moreover, both Cer 2 and Cer 5 occurred in Gaucher SC, whereas other Cer subfractions did not occur. These results indicate that two epidermal SM, that is, SM-1 and SM-3, are important precursors of two corresponding Cer in mammalian SC, that is, Cer 2 and Cer 5, but other Cer species, including the-hydroxy Cer species, do not derive from SM.
Biochemical and Biophysical Research Communications, 2021
Gros et al., Alteration of tyrosinase activity in human . . . , Melanoma Research, vol. 4, pp. 35... more Gros et al., Alteration of tyrosinase activity in human . . . , Melanoma Research, vol. 4, pp. 359-364, 1994.* Ucar, Kalust, The effect of histamine ..., Biochem. Biophy. Res. Commun. vol. 199/1, pp. 545–550, 1991.* Tomita et al Histamine Stimulate normal human melanocytes in vitro ..., J. Dermatol. Sci. Vol. 6/2, pp. 146-154, 1993.* C.-Melanocyte Stimulating hormone and its analogue Nle"DPhe'o-MSH affect morphology, tyrosinase activity and melanogenesis in cultured human melanocytes, by Gil lian Hunt et al., Journal of Cell Science 107,205–211 (1994). Abstracts From the 9" Annual Meeting of the Japanese Society for Pigment Cell Research, Pigment Cell Research 1994; 7:365-374 (2 pages). Histamine Stimulates normal human melanocytes in vitro: one of the possible inducers of hyperpigmentation in urti caria pigmentosa, by Yasushi Tomita et al., Journal of Der matological Science 6 (1993) 146-154. Endothelin-1 as a New Melanogen: Coordinated Expression of Its Gene and the ...
International Journal of Neuropsychopharmacology, 2016
scores. A linear regression analysis revealed that being male and married had significant positiv... more scores. A linear regression analysis revealed that being male and married had significant positive associations with sexual arousal, sexual satisfaction, and/or sexual desire, while the presence of TD and a longer duration of illness were associated with poor sexual arousal and/or sexual desire. Additionally, sexual function was significantly associated with SWN-K and DAI scores in multivariate analysis. Conclusions: The acknowledgement and management of sexual dysfunction in patients with schizophrenia by clinicians may be important for improvement of their quality of life and adherence to medication.
Deep ocean water has long been known for its stable characteristics of rich mineral ingredients, ... more Deep ocean water has long been known for its stable characteristics of rich mineral ingredients, a low water temperature, and chemical and bacteriological purity, but the effects of deep ocean water on skin physiology remain obscure. In this study, we examined how cultured human skin keratinocytes responded to exposure to deep ocean water from the coastal waters of Toyama Prefecture. We found that these waters promoted not only keratinocyte proliferation, but also the formation of cornified envelope in the process of keratinocyte maturation (differentiation) into cornified cells. After reviewing the mineral ingredients in the seawater, we concluded that silicate promoted this envelope formation, and that coexisting calcium accelerated the effect of the silicate. As the homeostasis of skin depends heavily on a balanced skin turnover, with finely tuned coordination between proliferation and differentiation, this deep ocean water from Toyama is expected to be useful for skin care.
Proceedings for Annual Meeting of The Japanese Pharmacological Society
Journal of Investigative Dermatology, 1998
Journal of Dermatological Science
The Journal of Dermatology
A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderm... more A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol‐induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism‐based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol‐induced leukoderma helps not only elucidate the mechanisms of non‐segmental vitiligo onset and progression, but also suggests prevention and treatment.
Experimental Dermatology
Although atopic dermatitis (AD) has been reported to be a typical type 2 immune response disease,... more Although atopic dermatitis (AD) has been reported to be a typical type 2 immune response disease, it is also an inflammatory skin disease that involves cytokines, such as Th1, Th17, and Th22. However, little is known about the mechanism by which the candidate cytokines, alone or in combination, are involved in AD pathology. Differences in cytokine balance, which contribute to the complexity of AD pathology, may influence the stratum corneum barrier function through tight junction (TJ) functional stability and contribute to disease severity. To confirm the regulatory mechanism of TJ protein expression in AD, we investigated the Th1 and Th17 pathways, which are the initiation factors of chronic AD pathology. We examined the effects of these cytokines on TJ protein expression in normal human epidermal keratinocytes in vitro. We also examined their function in a human skin-equivalent model. We observed a time- and dose-dependent inhibitory effect of claudin-1 on IFN-γ via the IFN-γ receptor/JAK/STAT signaling pathway. IFN-γ impaired TJ function in a human skin-equivalent model. Moreover, we investigated co-stimulation with IL-17A, which is highly expressed in AD skin lesions, and found that IL-17A restores IFN-γ-induced TJ dysfunction. This restoration of TJ function was mediated by atypical protein kinase C zeta activation without recovery of TJ protein expression. These results are informative for personalized AD treatment via systemic therapies using anti-cytokine antibodies and/or JAK inhibitors.
International Journal of Molecular Sciences
Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein tha... more Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that plays an important role in cancer metastasis and osteoblast differentiation. In the skin epidermis, GPNMB is mainly expressed in melanocytes and plays a critical role in melanosome formation. In our previous study, GPNMB was also found to be expressed in skin epidermal keratinocytes. In addition, decreased GPNMB expression was observed in the epidermis of lesional skin of patients with vitiligo. However, the exact role of keratinocyte-derived GPNMB and its effect on vitiligo is still unknown. In this study, we demonstrated that GPNMB expression was also decreased in rhododendrol-induced leukoderma, as seen in vitiligo. The extracellular soluble form of GPNMB (sGPNMB) was found to protect melanocytes from cytotoxicity and the impairment of melanogenesis induced by oxidative stress. Furthermore, the effect of rGPNMB was not altered by the knockdown of CD44, which is a well-known receptor...
The Journal of Dermatology
Biochemical and biophysical research communications, Jan 20, 2018
We have previously reported that HYBID (hyaluronan (HA)-binding protein involved in HA depolymeri... more We have previously reported that HYBID (hyaluronan (HA)-binding protein involved in HA depolymerization/KIAA1199/CEMIP) is a specific HA-binding protein that is essential for HA depolymerization in skin and synovial fibroblasts. HA is incorporated into cells in the presence of HYBID and clathrin, degraded in endosomes, and excreted into the extracellular space. However, it is not yet clear whether HYBID itself catalytically cleaves HA. A recent report on transmembrane protein 2 (TMEM2)-a novel cell surface hyaluronidase-prompted us to investigate whether TMEM2 is essential for HYBID-mediated HA depolymerization. In the present study, we found that transforming growth factor beta 1 (TGF-β1), which suppressed HA depolymerization with a concomitant decrease in HYBID expression, upregulated TMEM2 expression conversely in human skin fibroblasts. TMEM2 expression was not affected by histamine, which significantly increased HA depolymerization accompanied by an increase in HYBID expression...
Biochemical and biophysical research communications, Jan 27, 2018
HYBID (hyaluronan binding protein involved in hyaluronan [HA] depolymerization, KIAA1199/CEMIP) i... more HYBID (hyaluronan binding protein involved in hyaluronan [HA] depolymerization, KIAA1199/CEMIP) is a key player in HA depolymerization of the skin fibroblasts, arthritic synovial fibroblasts, and brain. Our previous study demonstrated that Hybid knock-out (KO) mice showed spatial memorial impairment, which is accompanied by the accumulation of high molecular weight HA in the hippocampus. However, the mechanism underlying cognitive impairment by Hybid deficiency remains unclear. In the present study, we examined the HA distribution patterns in the brains of wild-type (WT) and Hybid KO mice by HA staining using HA binding protein, and found that in Hybid KO mice, HA is accumulated and doublecortin-positive immature neurons are significantly decreased in the dentate gyrus of the hippocampus, where Hybid mRNA is highly expressed in WT mice. The Golgi-Cox staining demonstrated that the dendritic spine density is significantly decreased in the dentate gyrus granule cells in Hybid KO mice....
Neuroscience, Apr 7, 2017
HYBID (HYaluronan Binding Protein Involved in hyaluronan [HA] Depolymerization, KIAA1199) is one ... more HYBID (HYaluronan Binding Protein Involved in hyaluronan [HA] Depolymerization, KIAA1199) is one of the HA binding proteins that is involved in the depolymerization of HA. HYBID mRNA is highly expressed in the brain, however, the role of HYBID in the brain remains unclear. In this study, we bred Hybid knock-out (KO) mice and evaluated the function of Hybid in the central nervous system. Hybid mRNA was expressed in the brain, especially in the hippocampus and cerebellum, in wild-type mice. Hybid KO mice demonstrated decreased mnemonic ability in novel object recognition and Morris water maze tests. The average molecular mass of hippocampal HA increased in KO mice, accompanied by a significant increase in the total HA amount. Hybid KO mice did not differ in behavior from wild-type mice in the open field test, evaluation of acoustic startle responses, or drug-induced seizure test. In real-time PCR, Hyal1 and Hyal2 mRNA levels, which code hyaluronidases 1 and 2, respectively, did not di...