Subscribe to RSS
DOI: 10.1055/s-2001-13710
Differenzielle Muzinexpression im Gastrointestinaltrakt
Differential mucin expression in the gastrointestinal tractPublication History
10.10.2000
27.10.2000
Publication Date:
31 December 2001 (online)

Zusammenfassung
Muzine zeigen im physiologischen Zustand ein gewebespezifisches Expressionsmuster. Die wichtigsten Muzingene im Gastrointestinaltrakt sind MUC2, MUC3, MUC5AC und MUC6. MUC2 und MUC3 werden vorwiegend im Darm exprimiert, MUC5AC und MUC6 im Magen.
Pathophysiologische Zustände sind durch eine aberrante Expression von gewebsunspezifischen Muzinen und/oder eine reduzierte Expression gewebsspezifischer Muzine gekennzeichnet.
Hierbei überwiegt bei entzündlichen Prozessen die Koexpression von gewebsunspezifischen Muzinen. Bei neoplastischen Veränderungen findet sich ebenfalls eine aberrante Muzinexpression. Offensichtlich sind die prognostisch günstigeren Formen mit einer hohen aberranten Expression nichtspezifischer Muzine assoziiert. Bei prognostisch ungünstigeren Neoplasien findet sich, anscheinend als Ausdruck einer fortschreitenden Entdifferenzierung, eine reduzierte Expression dieser Muzine.
Bei dieser veränderten Muzinexpression spielen nicht nur posttranskriptionelle Veränderungen eine Rolle, auch die Muzingene können hier unterschiedlich reguliert sein.
Eine modifizierte Muzinexpression lässt auf einen pathophysiologischen Zustand schließen und kann die pathohistologische Diagnostik ergänzen.
Abkürzungen: MUC: Muzingen; NTR: non-tandem repeat; TR: tandem repeat
Differential mucin expression in the gastrointestinal tract
Under physiological conditions mucins display a tissue specific expression. MUC2, MUC3, MUC5AC and MUC6 are the major mucins in the gastrointestinal tract. In the intestinal tissue MUC2 and MUC3 are the predominant mucins, whereas MUC5AC and MUC6 are the most important mucins in the stomach.
Pathophysiological conditions are characterized by an aberrant gene expression. This includes the expression of non-tissue specific mucins as well as a reduced expression of the specific mucins. During inflammation a co-expression of non-tissue specific mucins was observed. Neoplastic transformations are also associated with an aberrant mucin expression. Obviously, an increased expression of non-specific mucins is related with a more favorable prognosis, while a decreased mucin expression is indicative for an increased cellular dedifferentiation and a poor prognosis. This modified mucin expression may result from a modified gene expression as well as from modifications in the posttranscriptional processing.
A modified mucin expression reflects pathophysiological conditions and may support the pathohistological diagnosis.
Abbreviations: MUC: Mucin Gene, NTR Non-tandem Repeat, TR Tandem Repeat
Schlüsselwörter
Muzine - MUC-Gene - Gastrointestinaltrakt - gastrointestinale Tumoren
Key words
Mucins - MUC-Genes - Gastrointestinal Tract - Gastrointestinal Neoplasia
Literatur
- 1 Forstner J F, Forstner G G. Gastrointestinal mucus. Johnson
LR Physiology of the gastrointestinal tract New
York; Raven
Press 1994: 1255-1283
MissingFormLabel
- 2 Neutra M R, Forstner J F. Gastrointestinal mucus: Synthesis, secretion, and
function. Johnson LR Physiology of the gastrointestinal
tract New York; Raven
Press 1987: 975-1009
MissingFormLabel
- 3
Allen A, Bell A, Mantle M, Pearson J P.
The structure and physiology of gastrointestinal
mucus.
Adv Exp Med
Biol.
1982;
144
115-133
MissingFormLabel
- 4
Allen A, Hutton D A, Leonard A J, Pearson J P, Sellers L A.
The role of mucus in the protection of the gastroduodenal
mucosa.
Scand J Gastroenterol
Suppl.
1986;
125
71-78
MissingFormLabel
- 5
Rose M C.
Mucins: Structure, function, and role in pulmonary
diseases.
Am J
Physiol.
1992;
263
L413-L429
MissingFormLabel
- 6
Strous G J, Dekker J.
Mucin-type glycoproteins.
Crit Rev Biochem Mol
Biol.
1992;
27
57-92
MissingFormLabel
- 7
Allen A, Leonard A.
Mucus structure.
Gastroenterol Clin
Biol.
1985;
9
9-12
MissingFormLabel
- 8
Carlstedt I, Sheehan J K.
Structure and macromolecular properties of mucus
glycoproteins.
Monogr
Allergy.
1988;
24
16-24
MissingFormLabel
- 9
Carlstedt I, Sheehan J K.
Macromolecular properties and polymeric structure of mucus
glycoproteins.
Ciba Found
Symp.
1984;
109
157-172
MissingFormLabel
- 10
Gum J R
Jr, Hicks J W, Toribara N W. et al .
The human MUC2 intestinal mucin has cysteine-rich subdomains
located both upstream and downstream of its central repetitive
region.
J Biol
Chem.
1992;
267
21 375-21 383
MissingFormLabel
- 11
Bell A E, Allen A, Morris E, Rees D A.
The structure of native gastric mucus gel.
Biochem
Soc
Trans.
1980;
8
716
MissingFormLabel
- 12
Sellers L A, Allen A, Morris E R, Ross-Murphy S B.
Mucus glycoprotein gels. Role of glycoprotein polymeric
structure and carbohydrate side-chains in gel-formation.
Carbohydr
Res.
1988;
178
93-110
MissingFormLabel
- 13
Dekker J, Aelmans P H, Strous G J.
The oligomeric structure of rat and human gastric
mucins.
Biochem J.
1991;
277 (Pt.
2)
423-427
MissingFormLabel
- 14
Gendler S J, Lancaster C A, Taylor-Papadimitriou J. et al .
Molecular cloning and expression of human tumor-associated
polymorphic epithelial mucin.
J Biol
Chem.
1990;
265
15 286-15 293
MissingFormLabel
- 15
Pemberton L, Taylor-Papadimitriou J, Gendler S J.
Antibodies to the cytoplasmic domain of the MUC1 mucin show
conservation throughout mammals.
Biochem Biophys Res
Commun.
1992;
185
167-175
MissingFormLabel
- 16
Gum J R Jr.
Human mucin glycoproteins: Varied structures predict diverse
properties and specific functions.
Biochem Soc
Trans.
1995;
23
795-799
MissingFormLabel
- 17
Gendler S J, Spicer A P.
Epithelial mucin genes.
Annu Rev
Physiol.
1995;
57
607-634
MissingFormLabel
- 18
Hakomori S.
Aberrant glycosylation in cancer cell membranes as focused on
glycolipids: overview and perspectives.
Cancer
Res.
1985;
45
2405-2414
MissingFormLabel
- 19
Hakomori S.
Tumor malignancy defined by aberrant glycosylation and
sphingo(glyco)lipid metabolism.
Cancer
Res.
1996;
56
5309-5318
MissingFormLabel
- 20
Hakomori S.
Aberrant glycosylation in tumors and tumor-associated
carbohydrate antigens.
Adv Cancer
Res.
1989;
52
257-331
MissingFormLabel
- 21
Egea G, Franci C, Gambus G. et al .
cis-Golgi resident proteins and O-glycans are abnormally
compartmentalized in the RER of colon cancer cells.
J Cell
Sci.
1993;
105 (Pt.
3)
819-830
MissingFormLabel
- 22
Carrato C, Balague C, de
Bolos C. et al .
Differential apomucin expression in normal and neoplastic
human gastrointestinal
tissues.
Gastroenterology.
1994;
107
160-172
MissingFormLabel
- 23
Bell A E, Allen A, Morris E, Rees D A.
Rheological studies on native pig gastric mucus
gel.
Adv Exp Med
Biol.
1982;
144
97-99
MissingFormLabel
- 24
Gendler S J, Burchell J M, Duhig T. et al .
Cloning of partial cDNA encoding differentiation and
tumor-associated mucin glycoproteins expressed by human mammary
epithelium.
Proc Natl Acad Sci
USA.
1987;
84
6060-6064
MissingFormLabel
- 25
Gendler S J, Cohen E P, Craston A. et al .
The locus of the polymorphic epithelial mucin (PEM) tumour
antigen on chromosome 1q21 shows a high frequency of alteration in primary
human breast tumours.
Int J
Cancer.
1990;
45
431-435
MissingFormLabel
- 26
Gum J R, Byrd J C, Hicks J W. et al .
Molecular cloning of human intestinal mucin cDNAs. Sequence
analysis and evidence for genetic polymorphism.
J Biol
Chem.
1989;
264
6480-6487
MissingFormLabel
- 27
Gum J R, Hicks J W, Kim Y S.
Identification and characterization of the MUC2 (human
intestinal mucin) gene 5’-flanking region: Promoter activity in cultured
cells.
Biochem J.
1997;
325 (Pt.
1)
259-267
MissingFormLabel
- 28
Gum J R
Jr, Hicks J W, Toribara N W, Siddiki B, Kim Y S.
Molecular cloning of human intestinal mucin (MUC2) cDNA.
Identification of the amino terminus and overall sequence similarity to
prepro-von Willebrand factor.
J Biol
Chem.
1994;
269
2440-2446
MissingFormLabel
- 29
Pigny P, Guyonnet-Duperat V, Hill A S. et al .
Human mucin genes assigned to 11p15.5: identification and
organization of a cluster of
genes.
Genomics.
1996;
38
340-352
MissingFormLabel
- 30
Fox M F, Lahbib F, Pratt W. et al .
Regional localization of the intestinal mucin gene MUC3 to
chromosome 7q22.
Ann Hum
Genet.
1992;
56 (Pt.
4)
281-287
MissingFormLabel
- 31
Gum J R, Hicks J W, Swallow D M. et al .
Molecular cloning of cDNAs derived from a novel human
intestinal mucin gene.
Biochem Biophys Res
Commun.
1990;
171
407-415
MissingFormLabel
- 32
Gum J R
Jr, Ho J JL, Pratt W S. et al .
MUC3 human intestinal mucin. Analysis of gene structure, the
carboxyl terminus, and a novel upstream repetitive region.
J Biol
Chem.
1997;
272
26 678-26 686
MissingFormLabel
- 33
Porchet N, Nguyen V C, Dufosse J. et al .
Molecular cloning and chromosomal localization of a novel
human tracheo-bronchial mucin cDNA containing tandemly repeated sequences of
48
base pairs.
Biochem Biophys Res
Commun.
1991;
175
414-422
MissingFormLabel
- 34
Gross M S, Guyonnet-Duperat V, Porchet N. et al .
Mucin 4 (MUC4) gene: Regional assignment (3q29) and RFLP
analysis.
Ann
Genet.
1992;
35
21-26
MissingFormLabel
- 35
Guyonnet D uperat
V, Audie J P, Debailleul V. et al .
Characterization of the human mucin gene MUC5AC: A consensus
cysteine-rich domain for 11p15 mucin genes?.
Biochem
J.
1995;
305 (Pt.
1)
211-219
MissingFormLabel
- 36
Buisine M P, Desseyn J L, Porchet N. et al .
Genomic organization of the 3’-region of the human
MUC5AC mucin gene: Additional evidence for a common ancestral gene for the
11p15.5 mucin gene family.
Biochem
J.
1998;
332
(Pt. 3)
729-738
MissingFormLabel
- 37
Ho S B, Roberton A M, Shekels L L. et al .
Expression cloning of gastric mucin complementary DNA and
localization of mucin gene
expression.
Gastroenterology.
1995;
109
735-747
MissingFormLabel
- 38
van de
Bovenkamp J H, Hau C M, Strous G J. et al .
Molecular cloning of human gastric mucin MUC5AC reveals
conserved cysteine-rich D-domains and a putative leucine zipper
motif.
Biochem Biophys Res
Commun.
1998;
245
853-859
MissingFormLabel
- 39
Dufosse J, Porchet N, Audie J P. et al .
Degenerate 87-base-pair tandem repeats create
hydrophilic/hydrophobic alternating domains in human mucin peptides mapped to
11p15.
Biochem J .
1993;
293 (Pt.
2)
329-337
MissingFormLabel
- 40
Desseyn J L, Aubert J P, Van
Senningen I, Porchet N, Laine A.
Genomic organization of the 3’ region of the human
mucin gene MUC5B.
J Biol
Chem.
1997;
272
16 873-16 883
MissingFormLabel
- 41
Desseyn J L, Buisine M P, Porchet N, Aubert J P, Laine A.
Genomic organization of the human mucin gene MUC5B. cDNA and
genomic sequences upstream of the large central exon.
J Biol
Chem.
1998;
273
30 157-30 164
MissingFormLabel
- 42
Desseyn J L, Guyonnet-Duperat V, Porchet N, Aubert J P, Laine A.
Human mucin gene MUC5B, the 10.7-kb large central exon
encodes various alternate subdomains resulting in a super-repeat. Structural
evidence for a 11p15.5 gene family.
J Biol
Chem.
1997;
272
3168-3178
MissingFormLabel
- 43
Keates A C, Nunes D P, Afdhal N H, Troxler R F, Offner G D.
Molecular cloning of a major human gall bladder mucin:
complete C-terminal sequence and genomic organization of
MUC5B.
Biochem J.
1997;
324 (Pt.
1)
295-303
MissingFormLabel
- 44
Offner G D, Nunes D P, Keates A C, Afdhal N H, Troxler R F.
The amino-terminal sequence of MUC5B contains conserved
multifunctional D domains: implications for tissue-specific mucin
functions.
Biochem Biophys Res
Commun.
1998;
251
350-355
MissingFormLabel
- 45
Toribara N W, Ho S B, Gum E. et al .
The carboxyl-terminal sequence of the human secretory mucin,
MUC6. Analysis of the primary amino acid sequence.
J Biol
Chem.
1997;
272
16 398-16 403
MissingFormLabel
- 46
Toribara N W, Roberton A M, Ho S B. et al .
Human gastric mucin. Identification of a unique species by
expression cloning.
J Biol
Chem.
1993;
268
5879-5885
MissingFormLabel
- 47
Biesbrock A R, Bobek L A, Levine M J.
MUC7 gene expression and genetic
polymorphism.
Glycoconj
J.
1997;
14
415-422
MissingFormLabel
- 48
Bobek L A, Liu J, Sait S N. et al .
Structure and chromosomal localization of the human salivary
mucin gene,
MUC7.
Genomics.
1996;
31
277-282
MissingFormLabel
- 49
Bobek L A, Tsai H, Biesbrock A R, Levine M J.
Molecular cloning, sequence, and specificity of expression of
the gene encoding the low molecular weight human salivary mucin
(MUC7).
J Biol
Chem.
1993;
268
20 563-20 569
MissingFormLabel
- 50
Shankar V, Pichan P, Eddy R L
Jr. et al .
Chromosomal localization of a human mucin gene (MUC8) and
cloning of the cDNA corresponding to the carboxy terminus.
Am J
Respir Cell Mol
Biol.
1997;
16
232-241
MissingFormLabel
- 51
Lapensee L, Paquette Y, Bleau G.
Allelic polymorphism and chromosomal localization of the
human oviductin gene (MUC9).
Fertil
Steril.
1997;
68
702-708
MissingFormLabel
- 52
Williams S J, McGuckin M A, Gotley D C. et al .
Two novel mucin genes down-regulated in colorectal cancer
identified by differential display.
Cancer
Res.
1999;
59
4083-4089
MissingFormLabel
- 53
Allen A, Flemstrom G, Garner A, Kivilaakso E.
Gastroduodenal mucosal protection.
Physiol
Rev.
1993;
73
823-857
MissingFormLabel
- 54
Allen A, Pearson J P, Blackburn A. et al .
Pepsins and the mucus barrier in peptic ulcer
disease.
Scand J Gastroenterol
Suppl.
1988;
146
50-57
MissingFormLabel
- 55
Van
Klinken B J, Dekker J, Buller H A, Einerhand A W.
Mucin gene structure and expression: Protection vs.
adhesion.
Am J
Physiol.
1995;
269
G613-G627
MissingFormLabel
- 56
Thornton D J, Khan N, Mehrotra R. et al .
Salivary mucin MG1 is comprised almost entirely of different
glycosylated forms of the MUC5B gene
product.
Glycobiology.
1999;
9
293-302
MissingFormLabel
- 57
Liu B, Rayment S, Oppenheim F G, Troxler R F.
Isolation of human salivary mucin MG2 by a novel method and
characterization of its interactions with oral bacteria.
Arch Biochem
Biophys.
1999;
364
286-293
MissingFormLabel
- 58
Khan S H, Aguirre A, Bobek L A.
In-situ hybridization localized MUC7 mucin gene expression to
the mucous acinar cells of human and MUC7-transgenic mouse salivary
glands.
Glycoconj
J.
1998;
15
1125-1132
MissingFormLabel
- 59
Bolscher J G, Groenink J, van
der Kwaak J S. et al .
Detection and quantification of MUC7 in submandibular,
sublingual, palatine, and labial saliva by anti-peptide antiserum.
J
Dent
Res.
1999;
78
1362-1369
MissingFormLabel
- 60
Moerk H, Scheurlen M, Al-Taie O. et al .
Characterization of Barrett’s and regenerative squamous
mucosa by MUC1 and MUC2 mRNA
expression.
Gastroenterology.
2000;
118
A226
MissingFormLabel
- 61
Labouvie C, Machado J C, Carneiro F. et al .
Differential expression of mucins and trefoil peptides in
native epithelium, Barrett’s metaplasia and squamous cell carcinoma of
the oesophagus.
J Cancer Res Clin
Oncol.
1999;
125
71-76
MissingFormLabel
- 62
Chinyama C N, Marshall R E, Owen W J. et al .
Expression of MUC1 and MUC2 mucin gene products in
Barrett’s metaplasia, dysplasia and adenocarcinoma: An immunopathological
study with clinical
correlation.
Histopathology.
1999;
35
517-524
MissingFormLabel
- 63
Ho S B, Shekels L L, Toribara N W. et al .
Mucin gene expression in normal, preneoplastic, and
neoplastic human gastric epithelium.
Cancer
Res.
1995;
55
2681-2690
MissingFormLabel
- 64
de
Bolos C, Garrido M, Real F X.
MUC6 apomucin shows a distinct normal tissue distribution
that correlates with Lewis antigen expression in the human
stomach.
Gastroenterology.
1995;
109
723-734
MissingFormLabel
- 65
Wagner S, Enss M L, Cornberg M. et al .
Morphological and molecular characterization of human gastric
mucous cells in long-term primary culture.
Pflugers
Arch.
1998;
436
871-881
MissingFormLabel
- 66
Cornberg M, Enss M L, Makkink M K. et al .
Variation of human mucin gene expression in gastric cancer
cell lines and gastric mucous cell primary cultures.
Eur J Cell
Biol.
1999;
78
832-841
MissingFormLabel
- 67
Ho S B, Niehans G A, Lyftogt C. et al .
Heterogeneity of mucin gene expression in normal and
neoplastic tissues.
Cancer
Res.
1993;
53
641-651
MissingFormLabel
- 68
Van Den
Brink G R, Tytgat K M, Van
Der Hulst R W. et al .
H pylori colocalises with MUC5AC in the human
stomach.
Gut.
2000;
46
601-607
MissingFormLabel
- 69
Byrd J C, Yan P, Sternberg L. et al .
Aberrant expression of gland-type gastric mucin in the
surface epithelium of Helicobacter pylori-infected
patients.
Gastroenterology.
1997;
113
455-464
MissingFormLabel
- 70
Byrd J C, Yunker C K, Xu Q S, Sternberg L R, Bresalier R S.
Inhibition of gastric mucin synthesis by Helicobacter
pylori.
Gastroenterology.
2000;
118
1072-1079
MissingFormLabel
- 71
Beil W, Enss M L, Muller S. et al .
Role of vacA and cagA in Helicobacter pylori inhibition of
mucin synthesis in gastric mucous cells.
J Clin
Microbiol.
2000;
38
2215-2218
MissingFormLabel
- 72
Van Klinken B J, Van
Dijken T C, Oussoren E. et al .
Molecular cloning of human MUC3 cDNA reveals a novel 59 amino
acid tandem repeat region.
Biochem Biophys Res
Commun.
1997;
238
143-148
MissingFormLabel
- 73
Buisine M P, Desreumaux P, Debailleul V. et al .
Abnormalities in mucin gene expression in Crohn’s
disease.
Inflamm Bowel
Dis.
1999;
5
24-32
MissingFormLabel
- 74
Chang S K, Dohrman A F, Basbaum C B. et al .
Localization of mucin (MUC2 and MUC3) messenger RNA and
peptide expression in human normal intestine and colon
cancer.
Gastroenterology.
1994;
107
28-36
MissingFormLabel
- 75
Weiss A A, Babyatsky M W, Ogata S, Chen A, Itzkowitz S H.
Expression of MUC2 and MUC3 mRNA in human normal, malignant,
and inflammatory intestinal tissues.
J Histochem
Cytochem.
1996;
44
1161-1166
MissingFormLabel
- 76
Bartman A E, Sanderson S J, Ewing S L. et al .
Aberrant expression of MUC5AC and MUC6 gastric mucin genes in
colorectal polyps.
Int J
Cancer.
1999;
80
210-218
MissingFormLabel
- 77
Ogata S, Uehara H, Chen A, Itzkowitz S H.
Mucin gene expression in colonic tissues and cell
lines.
Cancer
Res.
1992;
52
5971-5978
MissingFormLabel
- 78
Van
Klinken B J, Dekker J, van
Gool S A. et al .
MUC5B is the prominent mucin in human gallbladder and is also
expressed in a subset of colonic goblet cells.
Am J
Physiol.
1998;
274
G871-G878
MissingFormLabel
- 79
Buisine M P, Janin A, Maunoury V. et al .
Aberrant expression of a human mucin gene (MUC5AC) in
rectosigmoid villous
adenoma.
Gastroenterology.
1996;
110
84-91
MissingFormLabel
- 80
Tytgat K M, Van der
Wal J W, Einerhand A W, Buller H A, Dekker J.
Quantitative analysis of MUC2 synthesis in ulcerative
colitis.
Biochem Biophys Res
Commun.
1996;
224
397-405
MissingFormLabel
- 81
Balague C, Gambus G, Carrato C. et al .
Altered expression of MUC2, MUC4, and MUC5 mucin genes in
pancreas tissues and cancer cell
lines.
Gastroenterology.
1994;
106
1054-1061
MissingFormLabel
- 82
Terada T, Ohta T, Sasaki M, Nakanuma Y, Kim Y S.
Expression of MUC apomucins in normal pancreas and pancreatic
tumours.
J Pathol.
1996;
180
160-165
MissingFormLabel
- 83
Yonezawa S, Horinouchi M, Osako M. et al .
Gene expression of gastric type mucin (MUC5AC) in pancreatic
tumors: Its relationship with the biological behavior of the
tumor.
Pathol
Int.
1999;
49
45-54
MissingFormLabel
- 84
Balague C, Audie J P, Porchet N, Real F X.
In situ hybridization shows distinct patterns of mucin gene
expression in normal, benign, and malignant pancreas
tissues.
Gastroenterology.
1995;
109
953-964
MissingFormLabel
- 85
Hanski C, Hofmeier M, Schmitt-Graff A. et al .
Overexpression or ectopic expression of MUC2 is the common
property of mucinous carcinomas of the colon, pancreas, breast, and
ovary.
J Pathol.
1997;
182
385-391
MissingFormLabel
- 86
Yonezawa S, Sueyoshi K, Nomoto M. et al .
MUC2 gene expression is found in noninvasive tumors but not
in invasive tumors of the pancreas and liver: Its close relationship with
prognosis of the patients.
Hum
Pathol.
1997;
28
344-352
MissingFormLabel
- 87
Vandenhaute B, Buisine M P, Debailleul V. et al .
Mucin gene expression in biliary epithelial
cells.
J
Hepatol.
1997;
27
1057-1066
MissingFormLabel
- 88
Bartman A E, Buisine M P, Aubert J P. et al .
The MUC6 secretory mucin gene is expressed in a wide variety
of epithelial
tissues.
J Pathol.
1998;
186
398-405
MissingFormLabel
- 89
Ho S B, Shekels L L, Toribara N W. et al .
Altered mucin core peptide expression in acute and chronic
cholezystitis.
Dig Dis
Sci.
2000;
45
1061-1071
MissingFormLabel
- 90
Sasaki M, Nakanuma Y.
Frequent expression of MUC1 apomucin on biliary epithelial
cells of damaged small bile ducts in primary biliary cirrhosis and chronic
viral hepatitis: An immunohistochemical
study.
Hepatology.
1996;
23
1313-1317
MissingFormLabel
Anschrift für die Verfasser
Dr. Markus Cornberg
Abteilung Gastroenterologie and Hepatologie
Medizinische
Hochschule Hannover
30623 Hannover
Email: cornberg@gmx.de