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Yasuhiko Tomino - One of the best experts on this subject based on the ideXlab platform.

  • Th1 polarization in murine IgA nephropathy directed by bone marrow-derived cells. Commentary : Immune mechanisms beyond IgA mesangial deposition
    Kidney International, 2020
    Co-Authors: A. Rifai, Hitoshi Suzuki, Yusuke Suzuki, Takahiro Yamanaka, Satoshi Horikoshi, Masashi Aizawa, Masao Kihara, Huihua Pang, Yasuhiko Tomino
    Abstract:

    IgA nephropathy is the most common form of progressive glomerulonephritis although the pathophysiology of this nephropathy is unclear. The ddY Mouse is a spontaneous animal model with variable incidence and extent of glomerular injury mimicking human IgA nephropathy. Here, we transplanted bone marrow cells from 20-week-old ddY mice with beginning or quiescent IgA nephropathy into irradiated similar ddY mice, C57BI/6 (Th1 prone) mice, or BALB/c (Th2 prone) mice. Serum IgA/IgG complex and Th1/Th2 polarization of spleen cells was determined by enzyme-linked immunosorbent assay and confirmed by fluorescent cytometric analysis. The ddY mice with commencing IgA nephropathy demonstrated strong polarization toward Th1, while those with quiescent disease were Th2 polarized. Serum levels of IgA/IgG2a immune complex significantly correlated with the severity of the glomerular lesions. Bone marrow taken from mice with commencing IgA nephropathy conferred IgA nephropathy with Th1 polarization in recipient-quiescent mice, while transplantation from the quiescent mice ablated glomerular injury and mesangial IgA/IgG deposition in those commencing IgA disease. However, adoptive transfer of CD4 + T cells from those whose disease began failed to induce any IgA deposition or renal injury. Our study suggests that bone marrow cells, presuming IgA producing cells, may initiate this disease. Th1 cells may be involved in the pathophysiology of the disease after glomerular IgA deposition.

  • Development of Animal Models of Human IgA Nephropathy
    Drug Discovery Today: Disease Models, 2014
    Co-Authors: Hitoshi Suzuki, Yusuke Suzuki, Jan Novak, Yasuhiko Tomino
    Abstract:

    IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. IgAN is characterized by the mesangial accumulation of immune complexes containing IgA1, usually with co-deposits of complement C3 and variable IgG and/or IgM. Although more than 40 years have passed since IgAN was first described, the mechanisms underlying the disease development are not fully understood. Small-animal experimental models of IgAN can be very helpful in studies of IgAN, but development of these models has been hindered by the fact that only humans and hominoid primates have IgA1 subclass. Thus, multiple models have been developed, that may be helpful in studies of some specific aspects of IgAN. These models include a spontaneous animal model of IgAN, the ddY Mouse first reported in 1985. These mice show mild proteinuria without hematuria, and glomerular IgA deposits, with a highly variable incidence and degree of glomerular injury, due to the heterogeneous genetic background. To obtain a murine line consistently developing IgAN, we intercrossed an early-onset group of ddY mice, in which the development of IgAN includes mesangial IgA deposits and glomerular injury. After selective intercrossing for >20 generations, we established a novel 100% early-onset grouped ddY murine model. All grouped ddY mice develop proteinuria within eight weeks of age. The grouped ddY Mouse model can be a useful tool for analysis of multiple aspects of the pathogenesis of IgAN and may aid in assessment of some approaches for the treatment of IgAN.

  • Pathogenetic and therapeutic approaches to IgA nephropathy using a spontaneous animal model, the ddY Mouse
    Clinical and Experimental Nephrology, 2011
    Co-Authors: Yasuhiko Tomino
    Abstract:

    IgA nephropathy is the most common primary chronic glomerulonephritis in the world and was first described by Berger et al. (J Urol Nephrol 74:694–695;1968). Histopathologically, IgA nephropathy is characterized by expansion of the glomerular mesangial matrix with mesangial cell proliferation. Glomeruli typically contain generalized diffuse granular mesangial deposits of IgA (mainly IgA1), IgG and C3. In advanced patients, global glomerular sclerosis, crescent formation and tubulo-interstitial fibrosis are marked in light microscopy. IgA nephropathy is generally considered to be an immune-complex mediated glomerulonephritis. Although more than 40 years have passed since this disease was firstly described, the pathogenesis/initiation factors of IgA nephropathy are still obscure. The objective of this review is to explain the pathogenesis and treatment based on our previous data of ddY Mouse, a spontaneous animal model for IgA nephropathy.

  • spontaneous animal model ddY Mouse for studying the pathogenesis and treatment in patients with immunoglobulin a nephropathy
    Nephrology, 2010
    Co-Authors: Yasuhiko Tomino
    Abstract:

    : Immunoglobulin (Ig)A nephropathy has the highest incidence among the various forms glomerulonephritis in the world. The initiating and progressive factors in patients with IgA nephropathy are still obscure. Although there is no specific treatment for patients with IgA nephropathy at present, more clinical trials of new treatments are warranted for such patients. Therefore, it is necessary to clarify those factors and to develop more effective drugs using a spontaneous animal model, the ddY Mouse, in the future.

  • iga nephropathy lessons from an animal model the ddY Mouse
    Journal of Nephrology, 2008
    Co-Authors: Yasuhiko Tomino
    Abstract:

    Abstract IgA nephropathy is the most common primary chronic glomerulonephritis, and was first described by J. Berger (Transplant Proc. 1969;1:939-944). Histopathologically, IgA nephropathy is characterized by expansion of glomerular mesangial matrix, with mesangial cell proliferation. Glomeruli typically contain generalized-diffuse granular mesangial deposits of IgA, IgG and C3. Since pathogenesis of IgA nephropathy is still obscure, it is important to try to determine the initiation and progression of this disease using a suitable animal model. Several investigators, including Rifai's group (Rhode Island, USA) and Emancipator's group (Cleveland, Ohio, USA), reported various experimental animal models for this disease. In 1985, Imai et al first reported that the ddY strain of Mouse can serve as a spontaneous animal model for IgA nephropathy. These mice show mild proteinuria without hematuria, and mesangioproliferative glomerulonephritis with severe glomerular IgA deposits in association with an increase of serum IgA level (Imai et al. Kidney Int. 1985;27:756-761). Electron-dense deposits are observed in the glomerular mesangial areas by electron microscopy. Furthermore, Muso's group succeeded in generating a Mouse model of IgA nephropathy with a high incidence and early onset of glomerular IgA deposition (Miyawaki et al. Nephron. 1997;76:201-207). The selection procedure was successful in increasing the serum IgA level of the selected line. The selected ddY line (HIGA mice) showed only mild proteinuria (100-300 mg/dL) and did not show hematuria. These immunohistopathological findings in ddY mice resemble those in IgA nephropathy patients. The objectives of this review are to introduce the genetic background, Th1/Th2 polarization, expansion of extracellular matrices (ECMs) and treatment of IgA nephropathy of the ddY Mouse. These findings from the ddY Mouse appear to be useful in determining the pathogenesis and treatment of patients with IgA nephropathy.

Kazuhiko Hanada - One of the best experts on this subject based on the ideXlab platform.

  • Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer.
    BMC Cancer, 2020
    Co-Authors: Kazumi Sano, Kazuhiko Nakadate, Kazuhiko Hanada
    Abstract:

    BACKGROUND: While epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients' quality of life. This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Giotrif®), a second-generation EGFR-TKI, and established a skin disorder Mouse model to investigate the protective effect of minocycline. METHODS: First, under inhalation anesthesia with isoflurane, the back of a male ddY Mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder. RESULTS: Skin injury occurred on the back of the Mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the Mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically. CONCLUSIONS: These results suggest that minocycline petrolatum applied locally prevents and repairs afatinib-induced skin disorders of non-small cell lung cancer patients. Histological examination of skin has provided insights into the mechanism of the occurrence of afatinib-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

  • Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer
    2020
    Co-Authors: Kazumi Sano, Kazuhiko Nakadate, Kazuhiko Hanada
    Abstract:

    Abstract Abstract Background While epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients’ quality of life. Objective This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Geotrif®), a second-generation EGFR-TKI, and established a skin disorder Mouse model to investigate the protective effect of minocycline. Methods First, under inhalation anesthesia with isoflurane, the back of a male ddY Mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder. Results Skin injury occurred on the back of the Mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the Mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically. Discussion These results suggest that minocycline petrolatum applied locally prevents and repairs afatinib-induced skin disorders of non-small cell lung cancer patients. Histological examination of skin has provided insights into the mechanism of the occurrence of afatinib-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

  • Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer
    2020
    Co-Authors: Kazumi Sano, Kazuhiko Nakadate, Kazuhiko Hanada
    Abstract:

    Abstract Background While epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients' quality of life. Objective This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Geotrif®), a second-generation EGFR-TKI, and established a skin disorder Mouse model to investigate the protective effect of minocycline. Methods First, under inhalation anesthesia with isoflurane, the back of a male ddY Mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder. Results Skin injury occurred on the back of the Mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the Mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically. Discussion These results suggest that minocycline applied both locally and orally prevents and repairs afatinib-induced skin disorders. Histological examination of skin elucidated the mechanism of the occurrence of the EGFR-TKI-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

Ichiro Yamamoto - One of the best experts on this subject based on the ideXlab platform.

  • Establishment and characterization of transplantable tumor derived from a spontaneous malignant fibrous histiocytoma in the Mouse.
    Experimental Animals, 1996
    Co-Authors: Hiroaki Yamamoto, Ichiro Yamamoto
    Abstract:

    A tumor developed spontaneously in the subcutaneous tissue of the hind leg of a 7-month-old female ddY Mouse. Light and electron microscopical examinations revealed that the original tumor was composed of an admixture of fibroblast-like and histiocyte-like cells arranged predominantly in a storiform or cartwheel pattern. The tumor cells gave positive reactions for acid phosphatase, N-acetyl-β-glucosaminidase, non-specific esterase, β-glucuronidase, alpha-1 antitrypsin and fibronectin. The original tumor was diagnosed as a malignant fibrous histiocytoma (MFH). The tumor was serially transplanted into syngeneic mice up to the 92nd generation. The tumor was also consistently transplanted into allogeneic mice of several inbred strains. The allogeneic mice used in the present study were strains having different H-2 haplotypes. During succeeding passages, transplanted tumors showed aberrant growth properties. The tumor transplanted into mice of inbred strains took well to back transplantation for mice of original strain and allotransplantation for other inbred strains. The pathological features of these transplantable tumors were basically similar to those of the original tumor. As mentioned above, a MFH developed spontaneously in the ddY Mouse was consistently transplantable into both syngeneic and allogeneic mice.

  • allotransplantation of a spontaneous malignant fibrous histiocytoma in the ddY Mouse
    Experimental and Toxicologic Pathology, 1994
    Co-Authors: Hiroaki Yamamoto, Ichiro Yamamoto
    Abstract:

    Summary Malignant fibrous histiocytoma (MFH) developed spontaneously in the subcutaneous tissue of the hind leg of a 7-month-old female ddY Mouse. Histologically, an original tumor was composed of an admixture of fibroblast-like and histiocyte-like cells arranged in predominantly storiform or cartwheel pattern. The tumor was serially transplanted into syngeneic mice up to the 70th generation. Moreover, the tumor was also consistently transplanted into allogeneic mice of several inbred strains. Allogeneic mice used in the present study were 7 strains having the different H-2 haplotypes. During succeeding passages, transplanted tumor pieces showed aberrant growth properties. Histopathological features of these tumors were basically similar to original tumors. As mentioned above, a spontaneous MFH in the ddY Mouse was consistently transplantable into both syngeneic and allogeneic mice. The tumor was designated S-MFH-1T.

Kazumi Sano - One of the best experts on this subject based on the ideXlab platform.

  • Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer.
    BMC Cancer, 2020
    Co-Authors: Kazumi Sano, Kazuhiko Nakadate, Kazuhiko Hanada
    Abstract:

    BACKGROUND: While epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients' quality of life. This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Giotrif®), a second-generation EGFR-TKI, and established a skin disorder Mouse model to investigate the protective effect of minocycline. METHODS: First, under inhalation anesthesia with isoflurane, the back of a male ddY Mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder. RESULTS: Skin injury occurred on the back of the Mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the Mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically. CONCLUSIONS: These results suggest that minocycline petrolatum applied locally prevents and repairs afatinib-induced skin disorders of non-small cell lung cancer patients. Histological examination of skin has provided insights into the mechanism of the occurrence of afatinib-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

  • Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer
    2020
    Co-Authors: Kazumi Sano, Kazuhiko Nakadate, Kazuhiko Hanada
    Abstract:

    Abstract Abstract Background While epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients’ quality of life. Objective This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Geotrif®), a second-generation EGFR-TKI, and established a skin disorder Mouse model to investigate the protective effect of minocycline. Methods First, under inhalation anesthesia with isoflurane, the back of a male ddY Mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder. Results Skin injury occurred on the back of the Mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the Mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically. Discussion These results suggest that minocycline petrolatum applied locally prevents and repairs afatinib-induced skin disorders of non-small cell lung cancer patients. Histological examination of skin has provided insights into the mechanism of the occurrence of afatinib-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

  • Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer
    2020
    Co-Authors: Kazumi Sano, Kazuhiko Nakadate, Kazuhiko Hanada
    Abstract:

    Abstract Background While epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients' quality of life. Objective This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Geotrif®), a second-generation EGFR-TKI, and established a skin disorder Mouse model to investigate the protective effect of minocycline. Methods First, under inhalation anesthesia with isoflurane, the back of a male ddY Mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder. Results Skin injury occurred on the back of the Mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the Mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically. Discussion These results suggest that minocycline applied both locally and orally prevents and repairs afatinib-induced skin disorders. Histological examination of skin elucidated the mechanism of the occurrence of the EGFR-TKI-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

Takashi Mita - One of the best experts on this subject based on the ideXlab platform.

  • Differential up-regulation of voltage-dependent na+ channels induced by phenytoin in brains of genetically seizure-susceptible (el) and control (ddY) mic
    Neuroscience, 1994
    Co-Authors: Shunsuke Sashihara, Nobuyuki Yanagihara, Futoshi Izumi, Y. Murai, Takashi Mita
    Abstract:

    Abstract We investigated the effect of in vivo administration of an antiepileptic drug, phenytoin, on the saxitoxin binding capacity of receptor site 1 of the Na + channel α-subunit, and the expression activity of the channel messenger RNA in epileptic El Mouse brains, as compared with parental ddY mice. Subchronic treatment with phenytoin (25 mg/kg per day) for 14 days increased the [ 3 H]saxitoxin binding to brain-derived synaptic membranes of both El and control ddY mice in a time dependent manner. This increase plateaued at 21 ± 4% in El mice and 28 ± 3% in ddY control mice after administration of phenytoin for seven days. After cessation of treatment with phenytoin, [ 3 H]saxitoxin binding capacity returned to the basal level within two weeks in both ddY and El brains. Scatchard plot analysis revealed that the phenytoin treatment caused a 20–30% increase in maximum binding capacity of [ 3 H]saxitoxin binding without any change in equilibrium dissociation constant in the brain cortical synaptic membranes of both epileptic El and control ddY mice. A single injection of phenytoin (25 mg/kg) elevated the level of Na + channel messenger RNA within l h in ddY Mouse brains. The increase in Na + channel messenger RNA reached a peak (about 80% increase) after 5 h of phenytoin administration in a concentration-dependent manner (6.25–50 mg/kg). On the other hand, in El Mouse brains, Na + channel messenger RNA was not elevated until more than 5 h after phenytoin injection, and was increased by only about 33%. These results indicate that subchronic administration of phenytoin enhanced the expression of voltage-dependent Na + channel messenger RNA, which was followed by an increase in the number of Na + channels in both El and ddY mice. However, a single injection of phenytoin revealed a delayed expression of Na + channel messenger RNA in El Mouse brain, compared to ddY brains, suggesting that the molecular basis for up-regulation of Na + channels in epileptic El brains is abnormal.

  • Overproduction of voltage-dependent Na+ channels in the developing brain of genetically seizure-susceptible El mice
    Neuroscience, 1992
    Co-Authors: Shunsuke Sashihara, Nobuyuki Yanagihara, Hideyuki Kobayashi, Futoshi Izumi, S. Tsuji, Y. Murai, Takashi Mita
    Abstract:

    Abstract We used El mice, a ddY Mouse-derived, autosomal mutant strain and a model of hereditary sensory-precipitated epilepsy, to test the hypothesis that epileptic susceptibility may be associated with the activity of voltage-dependent ion channels. We examined the saxitoxin binding capacity of the receptor site 1 of the Na + channel α-subunit, the expression activity of the Na + channel mRNA, the veratridine-induced 22 Na + influx in the brain synaptosomes, and the regional distribution of Na + channels in the brain. Compared with control ddY mice, in El mice which have not experienced seizures, the number of Na + channels in the brain synaptosomes increased by approximately 20% starting at the fourth postnatal week through the adult stage as determined by [ 3 H]saxitoxin binding assay. Northern blot hybridization analysis showed excess expression of Na + channel mRNA (by 30–40%) coincidentally with Na + channel increases. Regional analysis using the saxitoxin binding assay demonstrated approximately 1.3-fold denser distribution of Na + channels in the cortex and cerebellum but not the hippocampus and midbrain including thalamus of El mice compared to ddY mice. Scatchard plot analysis for saxitoxin binding in the cortex of El Mouse brains revealed higher maximum binding capacity (B max ) values (ddY, 4.43 ± 0.28pmol/mg protein; El,5.43 ± 0.25pmol/mg protein) without a change in K d (ddY, 1.05 ± 0.03nM; El,1.03 ± 0.01nM). Lastly, veratridine-evoked 22 Na + influx, sensitive to tetrodotoxin, was increased approximately 45% in the cortical synaptosomes in six-week-old El mice. These results suggest that El brains characteristically produce an excess of voltage-dependent Na + channels which is responsible for hyperexcitability of the central nervous system and may account for the predisposition of El mice to epileptic seizures.

  • Biochemical Abnormalities in Developing El Mouse
    Psychiatry and Clinical Neurosciences, 1991
    Co-Authors: Shunsuke Sashihara, Ikuho Aramaki, Yoshiyuki Murai, Takashi Mita
    Abstract:

    Summary Complex biochemical abnormalities were found in the early developmental stage of the El Mouse. First, the El Mouse has abnormal levels of specific amino acid concentration within a week from birth. Second, an unusual expression of poly(A)+ RNA from the one-day newborn liver of the El Mouse was detected by use of Cot 100 DNA as a probe. Third, sodium channels are increased in synaptosomes and at the mRNA expression level of the 3 or 4-week-old El Mouse brains, compared with the ddY Mouse. These results suggest that the biochemical abnormalities described in this study may affect greatly the epileptogenesis of El Mouse.