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034 Narrowing the Darier's disease region on chromosome 12q and exclusion of candidate genes by linkage analysis and fish
JSID Abstracts
187
HLA-A'0207 GENE CONTROLLING THE SUSCEPTIBILITY To PSORIATIC ARTHRITIS. N. Muto”, M. Ichimiya', H. 'rateno', H. Fwxmoto', H. Takahata', C. Asagami'and A. Kimuraz. 'Department of Dermatology, Yamaguchi University School of Medicine, Ube, Japan. '&partment of Tissue Physiology, Tokyo Medical and Dental University. Tokyo, Japan. We reported a strong association between HIA-A2(-B46-DRBOQ6) and the susceptibility to psoriatic arthritis (PA), by using a Japanese population (Tissue Antigens, 45:362, 1995). In order to elucidate a true susceptibility gene involved in the developnat of PA, we investigated polynwrphisms of BLAA2 alleles, by using PCR-SSOP method. The present study PA. involved 24 patients with The frequency of HLA-A*0207 was significantly increased in PA (relative risk = 9.4; corrected P < 0.01). In contrast, the frequencies Of F&A-A*0201 and A’0206 did not differ significantly from that of normal control. We conclude that the true susceptibility gene involved in the development of PA might be the HLA-A.0207.
NARRWING THE DARIER S DISEASE REGION ON CHROllOSfME 124 AND EXCLUSION OF CANDIDATE GENES BY LINKAGE ANALYSIS AND FISH. lkeda 8.“. Ogaua H”, Epstein Jr Et? and Coldwith LAJ’ bepartnents of Dermatology, “Juntendo University, School of Medicine, Japan. “University of California at San Francisco, USA and “University of Rochester. USA. We have previously reoorted.that 0arier.s disease gene (DAR) IS located on chronmscme 12 (12q23-24.1) between 012884 and D12S354. We data for all kindreds and found that 3 further analvsed haplotyoe individuals from 3 independent pedigrees shcuad reccmbinations at fran a separate family showed recaeb~01X5129 and that 1 individual nation at 012S234, having narrowed the localization of the dtsease gene to a re.zion of less than 3.8 cM between 0125234 and 012S129. By fluorescent in situ hybridization (FISH) analysis. the estia!ated physical distance between these two markers was 2-.5 megabase. In addition, NO synthase 1, a candidate gene supposed to be in this region, was excluded from DAR by linkage ana!ysis. We are no+u exaining whether or not other candidate genes such as oaxillin and serine/threonine protein phosohatase are truly located between D12S129 and 012S234 by two color FISH analysis.
032 DISTRIRUTION OF TRANSGLUTAMINASE 1 (TGaseK) IN THE EPIDERMIS OF HARLEQUIN ICHTHYOSIS.
035
M. AkivamcQ, H. Shimizul. S.-Y. Kims, K. Yonedad. T. Nishikawa’. ‘Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. ?Division of Dermatology. Kitasato Institute Hospital. Tokyo, Japan. ‘Pacific Corp. R & D Center. Kyounggi-do, Korea. Qepartment of Dermatology. Kyoto University Faculty of Medicine, Kyoto. Japan. Both harlequin ichthyosis (HI) and lamellar ichthyosis (LI) are among the most severe types of congenital ichthyoses and there is a controversy over the differences between HI and LI. Recently. defect of keratinocyte transglutaminase (TGaseK,, transglutaminase I (TGasel)) directly caused by its responsible gene has been reported in some cases of LI. We analyzed the distribution of TGasel in the epidermis of two newborn Japanese male with HI. lmmunohistochemical labeling showed that TGasel was distributed in the entire epidermis of lesional skin with some potentiation in the granular layer. This distribution pattern indicates that TGasel is normally expressed in HI, thus suggesting a different pathogenesis of HI from Ll cases in which abnormal TGasel is confirmed.
PROMOTING FACTORS FOR BASEMENT MEMBRANE FORMATION IN /N VITRO SKIN MODELS: EFFECT OF FETAL SKIN KERATINOCYTES. T.*‘. M T unena!‘. N. Akutu’, R. Brunt? a& R.E. Burreao&.‘Shixido iii Science Reserach Labomtorirr. Yokohama. Japan. 2MGHIHarvard Cutaneous Biology Rrsearch Center. Boston. USA. III rsirm model\ of ckin development utllizmg krratinocyreh grown upon fihrobln\t-contracted collagrn gela havs been known lo uccumulalr ba\rmmt membrane (BM) component\ al krrurinocyte-gel junction. If is still obacurc which drrmal-epidcrmal (D-E) intrractmn?, regulate the synthrsi\ and deposition of BM component> and which BM componenlr catalyze a\hcmbly. To elucidate D-E mfcrac(mn< required to ths BM formatloo. dual cukurcs of fetal huvinc kemunocylrs (FBK) und human foreskin fibroblssta (HF). or human foreskin keratinocy(e\ (HK) and HF wrre analyzed by bpecics specific antlbodles and electron microscopy. In culture of HK and HP, we ohbcrved that: (I) kalinin. lamininl. type IV collagrn and type VII collagen wcrc depobiced at krratinocytc-gel .juncrion. but BM ~micturcs wrrr poorly organimd: (2) TGF-PI enhanced production of BM componenl\. but no cffcct on BM \rructures. In cullurc of FBK and HF. we observed that. (I) BM componenrs were synthesized by both cells and deposited at kcratlnocyte-gel junctmn:(2) BM btm~lurt‘s were formed with few unchoring fihrils. Thcsc rcbulls indicate that BM slru~fures are formed in \kin models urilizlng diffc~enr spec~c\ cells end thal fetal krratmocytm promorr BM forma&m.
036
033 ABNORMAL LIPID COMPOSITION IN SCALES, RED BLOOD CELLS AND PLASMA FROM A PATIENT WITH STEROID
THE BASEMENT RECONSTRUCTED
SULFATASE DEFICIENCY. S.,gana*l. Otsuka 2. Department of Dermatology,
N. Ishiil, H. Nakaiima~, M. Tsunenagaz,To. Nishivamaz. lDepartment of Dcrmatology,Yokohama Ciity University School of Medic&Yokohama, Japan. %ife Science Research Laboratories,Shiseido Research
M. Ujlharal sod F. ‘Yarnaguchi Rosai
Yamaguchl, 2Unlversity of Tsukuba, Ibaragl, Japan. The lipid contents of scales, red blood cells and plasma of a patient with steroid sulfatase deficiency were analyzed. The patient’s scales accumulated cholesterol sulfate but decreased free sterols, stem1 esters and ceramldes, and lacked phospholiplds. The s&es also contained fatty acids showing insufficient chain elongation. The patienrs red blood cells or plasma accumulated cholesteml sulfate wlthout abnormalities of other lipid compositions. The abnormal lipid composition of scales may contrlbute to the pathogenesis of generalized Hospital,
hyperkeratosis
In the disease.
MEMBRANE COMPONENTS OF THE SKIN MODEL. Ta. Nishivama*l, T. Sasaki~,
Center,YokohamaJa. We have investigated the basement membrane components of reconstructed skin model in order to establish a research system of human skin in viva. A 3-dimensional rcconstructcd skin model was made through simultaneous culture of normal human skin fibroblasts and keratinocytes. The skin model was implanted onto SCID mouse skin and morphological and immunohistuchemical changes of this skin model was compared bcwccn cultured (in vitro) and transplanted (in viva) skin as a time comsc study. We could recognize type Iv and VP collagen expression in viva. On the other hand, we muld hardly remgnizc the
expression in vitro. These results suggest that the basement membrane components may be induced in the skin model by some factor(s) from the SCID mice.
187
HLA-A'0207 GENE CONTROLLING THE SUSCEPTIBILITY To PSORIATIC ARTHRITIS. N. Muto”, M. Ichimiya', H. 'rateno', H. Fwxmoto', H. Takahata', C. Asagami'and A. Kimuraz. 'Department of Dermatology, Yamaguchi University School of Medicine, Ube, Japan. '&partment of Tissue Physiology, Tokyo Medical and Dental University. Tokyo, Japan. We reported a strong association between HIA-A2(-B46-DRBOQ6) and the susceptibility to psoriatic arthritis (PA), by using a Japanese population (Tissue Antigens, 45:362, 1995). In order to elucidate a true susceptibility gene involved in the developnat of PA, we investigated polynwrphisms of BLAA2 alleles, by using PCR-SSOP method. The present study PA. involved 24 patients with The frequency of HLA-A*0207 was significantly increased in PA (relative risk = 9.4; corrected P < 0.01). In contrast, the frequencies Of F&A-A*0201 and A’0206 did not differ significantly from that of normal control. We conclude that the true susceptibility gene involved in the development of PA might be the HLA-A.0207.
NARRWING THE DARIER S DISEASE REGION ON CHROllOSfME 124 AND EXCLUSION OF CANDIDATE GENES BY LINKAGE ANALYSIS AND FISH. lkeda 8.“. Ogaua H”, Epstein Jr Et? and Coldwith LAJ’ bepartnents of Dermatology, “Juntendo University, School of Medicine, Japan. “University of California at San Francisco, USA and “University of Rochester. USA. We have previously reoorted.that 0arier.s disease gene (DAR) IS located on chronmscme 12 (12q23-24.1) between 012884 and D12S354. We data for all kindreds and found that 3 further analvsed haplotyoe individuals from 3 independent pedigrees shcuad reccmbinations at fran a separate family showed recaeb~01X5129 and that 1 individual nation at 012S234, having narrowed the localization of the dtsease gene to a re.zion of less than 3.8 cM between 0125234 and 012S129. By fluorescent in situ hybridization (FISH) analysis. the estia!ated physical distance between these two markers was 2-.5 megabase. In addition, NO synthase 1, a candidate gene supposed to be in this region, was excluded from DAR by linkage ana!ysis. We are no+u exaining whether or not other candidate genes such as oaxillin and serine/threonine protein phosohatase are truly located between D12S129 and 012S234 by two color FISH analysis.
032 DISTRIRUTION OF TRANSGLUTAMINASE 1 (TGaseK) IN THE EPIDERMIS OF HARLEQUIN ICHTHYOSIS.
035
M. AkivamcQ, H. Shimizul. S.-Y. Kims, K. Yonedad. T. Nishikawa’. ‘Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. ?Division of Dermatology. Kitasato Institute Hospital. Tokyo, Japan. ‘Pacific Corp. R & D Center. Kyounggi-do, Korea. Qepartment of Dermatology. Kyoto University Faculty of Medicine, Kyoto. Japan. Both harlequin ichthyosis (HI) and lamellar ichthyosis (LI) are among the most severe types of congenital ichthyoses and there is a controversy over the differences between HI and LI. Recently. defect of keratinocyte transglutaminase (TGaseK,, transglutaminase I (TGasel)) directly caused by its responsible gene has been reported in some cases of LI. We analyzed the distribution of TGasel in the epidermis of two newborn Japanese male with HI. lmmunohistochemical labeling showed that TGasel was distributed in the entire epidermis of lesional skin with some potentiation in the granular layer. This distribution pattern indicates that TGasel is normally expressed in HI, thus suggesting a different pathogenesis of HI from Ll cases in which abnormal TGasel is confirmed.
PROMOTING FACTORS FOR BASEMENT MEMBRANE FORMATION IN /N VITRO SKIN MODELS: EFFECT OF FETAL SKIN KERATINOCYTES. T.*‘. M T unena!‘. N. Akutu’, R. Brunt? a& R.E. Burreao&.‘Shixido iii Science Reserach Labomtorirr. Yokohama. Japan. 2MGHIHarvard Cutaneous Biology Rrsearch Center. Boston. USA. III rsirm model\ of ckin development utllizmg krratinocyreh grown upon fihrobln\t-contracted collagrn gela havs been known lo uccumulalr ba\rmmt membrane (BM) component\ al krrurinocyte-gel junction. If is still obacurc which drrmal-epidcrmal (D-E) intrractmn?, regulate the synthrsi\ and deposition of BM component> and which BM componenlr catalyze a\hcmbly. To elucidate D-E mfcrac(mn< required to ths BM formatloo. dual cukurcs of fetal huvinc kemunocylrs (FBK) und human foreskin fibroblssta (HF). or human foreskin keratinocy(e\ (HK) and HF wrre analyzed by bpecics specific antlbodles and electron microscopy. In culture of HK and HP, we ohbcrved that: (I) kalinin. lamininl. type IV collagrn and type VII collagen wcrc depobiced at krratinocytc-gel .juncrion. but BM ~micturcs wrrr poorly organimd: (2) TGF-PI enhanced production of BM componenl\. but no cffcct on BM \rructures. In cullurc of FBK and HF. we observed that. (I) BM componenrs were synthesized by both cells and deposited at kcratlnocyte-gel junctmn:(2) BM btm~lurt‘s were formed with few unchoring fihrils. Thcsc rcbulls indicate that BM slru~fures are formed in \kin models urilizlng diffc~enr spec~c\ cells end thal fetal krratmocytm promorr BM forma&m.
036
033 ABNORMAL LIPID COMPOSITION IN SCALES, RED BLOOD CELLS AND PLASMA FROM A PATIENT WITH STEROID
THE BASEMENT RECONSTRUCTED
SULFATASE DEFICIENCY. S.,gana*l. Otsuka 2. Department of Dermatology,
N. Ishiil, H. Nakaiima~, M. Tsunenagaz,To. Nishivamaz. lDepartment of Dcrmatology,Yokohama Ciity University School of Medic&Yokohama, Japan. %ife Science Research Laboratories,Shiseido Research
M. Ujlharal sod F. ‘Yarnaguchi Rosai
Yamaguchl, 2Unlversity of Tsukuba, Ibaragl, Japan. The lipid contents of scales, red blood cells and plasma of a patient with steroid sulfatase deficiency were analyzed. The patient’s scales accumulated cholesterol sulfate but decreased free sterols, stem1 esters and ceramldes, and lacked phospholiplds. The s&es also contained fatty acids showing insufficient chain elongation. The patienrs red blood cells or plasma accumulated cholesteml sulfate wlthout abnormalities of other lipid compositions. The abnormal lipid composition of scales may contrlbute to the pathogenesis of generalized Hospital,
hyperkeratosis
In the disease.
MEMBRANE COMPONENTS OF THE SKIN MODEL. Ta. Nishivama*l, T. Sasaki~,
Center,YokohamaJa. We have investigated the basement membrane components of reconstructed skin model in order to establish a research system of human skin in viva. A 3-dimensional rcconstructcd skin model was made through simultaneous culture of normal human skin fibroblasts and keratinocytes. The skin model was implanted onto SCID mouse skin and morphological and immunohistuchemical changes of this skin model was compared bcwccn cultured (in vitro) and transplanted (in viva) skin as a time comsc study. We could recognize type Iv and VP collagen expression in viva. On the other hand, we muld hardly remgnizc the
expression in vitro. These results suggest that the basement membrane components may be induced in the skin model by some factor(s) from the SCID mice.