SUH BXD Liver CCl4-treated Affy Mouse Gene 1.0 ST Exon Level (Jun11) RMA

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Saarland University Homburg (SUH) Carbon Tetrachloride-Treated BXD Mouse Affymetrix Mouse Gene 1.0 ST Array data set

This experimental liver gene expression data set (~100 Affymetrix exon-type arrays), was generated by Frank Lammert, Sonja Hillebrandt, Rabea Hall, and colleagues at the Saarland University Medical Center in Homburg, Germany. This work is part of the German Network for Systems Genetics (GeNeSys).

Expression data after carbon tetrachloride treatment (CCl4, also known as Halon, Freon, carbon tet, or tetrachloromethane) were generated using RNA sample from 30 BXD strains, both parental strains (C57BL/6J, DBA/2J), and B6D2 F1 hybrids. The great majority of cases were females and were treated with carbon tetrachloride injections over a six week period. Three arrays were run for each strain using independent liver samples.

PURPOSE: The overall goal of the project is to understand the etiology of liver fibrogenesis using carbon tetracholoride as a toxin and inducer of liver disease. Liver fibrogenesis, or scarring of the liver, is the common end-stage of chronic liver diseases, in particular after chronic viral infections. In Germany along complications associated with liver fibrosis cause approximately 10,000 deaths per year. In the past decade key molecular pathomechanisms of hepatic fibrogenesis due to chronic viral infections have been identified. Activated hepatic stellate cells (HSCs) drive the process of de novo deposition of abnormal extracellular matrix, which is modulated by complex interactions between cytokines, receptors, and matrix components.

Several studies have demonstrated that the course and progression of the fibrogenic response to chronic liver injury is highly variability among individuals. This marked variabilityhas been attributed to etiology, age, gender, and environmental factors. In humans these genetic disease fibrosis predisposition factors have not yet to be studied systematically.

Our group recently identified a gene variant that contributes to liver fibrogenesis by using QTL mapping in an experimental crosses between fibrosis-susceptible and resistant strains of mice (Hillebrandt et al., 2005). We demonstrated that sequence differences in the HC gene that encodes complement factor C5 (also known as hemolytic complement), are responsible for this strain difference. Common haplotype-tagging polymorphisms of the human HC gene were shown to be associated with advanced fibrosis in chronic hepatitis C virus infection. Thus, the mouse analysis led to the identification of an unknown gene underlying human susceptibility to liver fibrosis, supporting the idea that HC has a causal role in chronic inflammatory disorders and organ fibrogenesis across species.

As part of the GeNeSys program we have studied liver fibrogenesis in the BXD family of strains as a model for chronic liver injury. This expression data set is used to map complex genetic traits that modulate gene expression and determine gene networks during liver fibrogenesis in GRPs.

The following assays are complete or are in progress:

  1. Liver fibrosis studies: Phenotyping protocols include standard histology, morphometry, biochemical quantification of hepatic collagen contents, serum surrogate markers of fibrosis, immunohistochemistry, and expression profiling of proinflammatory and profibrogenic genes by qRT-PCR and Affymetrix microarrays (this data set).
  2. Characterization of liver cells: Liver immune cell fractions will be isolated and sorted according to SOPs developed in the Lammert laboratory. In addition, in cooperation with the technology platforms of the HepatoSys Network of Excellence, we will characterize primary HSCs that play critical roles in liver fibrogenesis with respect to proinflammatory responses during chronic liver inflammation.

PROTOCOL for carbon tetrachloride (CCl4) treatment (parental strains, F1, and BXD lines). Animals were injected with CCl4 (12 x 0.7 mg/kg ip) over a 6-week period on days 1 and 4 of each week. Intraperitoneal injections were begun between the ages of 6-8 weeks. Animals were sacrificed after 6 weeks of treatment at 12 to 14 weeks of age. Untreated control mice from only the two parental strains were also sacrificed at 12-14 weeks of age

About tissue

Tissue: Livers were snap frozen in liquid nitrogen immediately after harvesting. RNA was extracted and submitted to the UTHSC Molecular Resource Core for expression profiling. Expression data were generated by Lorne Rose, William Taylor and colleagues. Data were entered into GeneNetwork by Arthur Centeno, June 17, 2011. Data were quality controlled by R. W. Williams.

About data processing

QC Results: This data set consists of expression data for 33 strains. A total of 166 probe sets are associated with LOD scores above 10 and the highest linkage score of 22 for Rpl3 (probe set 10430669). Strain distribution patterns of eQTLs with a Mendelian expression pattern match those of their closest markers perfectly, verifying that there are no errors of strain assignment in this data set.

Analysis of XIST probe set 1060617 confirms that most strains are purely female. However, only males were available for BXD1 and BXD6. BXD28 and BXD33 data are based on the average of two female samples and one male sample. All other strains are purely female.

Data were analyzed by Rabea Hall and Dr. Frank Lammert at the Universitätsklinikum des Saarlandes in Homburg, Germany.

Contacts: rabea.hall at, Rabea.Hall at, and frank.lammert at

Table updated 7-19-2011

Index Sample ID Strain ID Treatment
1 504 B6D2F1 CCl4
2 506 B6D2F1 CCl4
3 508 B6D2F1 CCl4
4 414 C57BL/6J CCl4
5 488 C57BL/6J CCl4
6 489 C57BL/6J CCl4
7 B6J1 C57BL/6J untreated control
8 B6J2 C57BL/6J untreated control
9 B6J3 C57BL/6J untreated control
10 449 DBA/2J CCl4
11 450 DBA/2J CCl4
12 451 DBA/2J CCl4
13 219.1 DBA/2J untreated control
14 219.2 DBA/2J untreated control
15 219.3 DBA/2J untreated control
16 276 BXD1 CCl4
17 278 BXD1 CCl4
18 279 BXD1 CCl4
19 353 BXD2 CCl4
20 357 BXD2 CCl4
21 358 BXD2 CCl4
22 272 BXD6 CCl4
23 273 BXD6 CCl4
24 274 BXD6 CCl4
25 405 BXD11 CCl4
26 406 BXD11 CCl4
27 408 BXD11 CCl4
28 239 BXD12 CCl4
29 240 BXD12 CCl4
30 241 BXD12 CCl4
31 553 BXD13 CCl4
32 554 BXD13 CCl4
33 555 BXD13 CCl4
34 249 BXD14 CCl4
35 250 BXD14 CCl4
36 288 BXD14 CCl4
37 191 BXD19 CCl4
38 644 BXD19 CCl4
39 645 BXD19 CCl4
40 442 BXD24a CCl4
41 443 BXD24a CCl4
42 444 BXD24a CCl4
43 216 BXD27 CCl4
44 218 BXD27 CCl4
45 290 BXD27 CCl4
46 28 BXD28 CCl4
47 71 BXD28 CCl4
48 129 BXD28 CCl4
49 219 BXD31 CCl4
50 220 BXD31 CCl4
51 231 BXD31 CCl4
52 549 BXD32 CCl4
53 550 BXD32 CCl4
54 551 BXD32 CCl4
55 139 BXD33 CCl4
56 140 BXD33 CCl4
57 559 BXD33 CCl4
58 132 BXD34 CCl4
59 146 BXD34 CCl4
60 147 BXD34 CCl4
61 293 BXD39 CCl4
62 597 BXD39 CCl4
63 599 BXD39 CCl4
64 154 BXD40 CCl4
65 570 BXD40 CCl4
66 572 BXD40 CCl4
67 361 BXD42 CCl4
68 362 BXD42 CCl4
69 373 BXD42 CCl4
70 428 BXD43 CCl4
71 429 BXD43 CCl4
72 556 BXD43 CCl4
73 472 BXD51 CCl4
74 473 BXD51 CCl4
75 474 BXD51 CCl4
76 533 BXD55 CCl4
77 534 BXD55 CCl4
78 535 BXD55 CCl4
79 519 BXD62 CCl4
80 520 BXD62 CCl4
81 521 BXD62 CCl4
82 463 BXD65 CCl4
83 464 BXD65 CCl4
84 465 BXD65 CCl4
85 327 BXD69 CCl4
86 346 BXD69 CCl4
87 347 BXD69 CCl4
88 614 BXD73 CCl4
89 616 BXD73 CCl4
90 619 BXD73 CCl4
91 395 BXD75 CCl4
92 482 BXD75 CCl4
93 483 BXD75 CCl4
94 317 BXD87 CCl4
95 319 BXD87 CCl4
96 322 BXD87 CCl4
97 374 BXD90 CCl4
98 388 BXD90 CCl4
99 389 BXD90 CCl4
100 402 BXD96 CCl4
101 403 BXD96 CCl4
102 404 BXD96 CCl4
103 584 BXD98 CCl4
104 585 BXD98 CCl4
105 607 BXD98 CCl4