Beefing up resistance to mad cow disease

Summaries of newsworthy papers from Nature Research Journals include New breast cancer susceptibility gene identified, Evidence for a stem cell origin of cancer, Genetic risk factor for Crohn disease found and Tolerating the gut


For papers that will be published online on 31 December 2006

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Beefing up resistance to mad cow disease – Nature Biotechnology

New breast cancer susceptibility gene identified – Nature Genetics

Evidence for a stem cell origin of cancer – Nature Genetics

Genetic risk factor for Crohn disease found – Nature Genetics

Tolerating the gut – Nature Immunology

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of Press contacts for the Nature journals are listed at the end of this release.

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**********************************NATURE BIOTECHNOLOGY************************

[1] Beefing up resistance to mad cow disease
DOI: 10.1038/nbt1271

A team of American and Japanese scientists have generated cows that lack the protein responsible for mad cow disease according to a report in the January issue of Nature Biotechnology. A thorough clinical examination of the animals up to the age of 20 months indicates that they are healthy, and laboratory tests of their brain tissue suggests that they are likely to be resistant to mad cow disease, which can be transmitted to humans through consumption of affected beef.

Mad cow disease (or bovine spongiform encephalopathy) is caused by a misfolded form of a particular protein known as a ‘prion’ protein. Kuroiwa and colleagues genetically engineered cows that are identical to ordinary cows except that they lack the prion protein. Because scientists don’t understand the function of this protein in its correctly folded form, it was unclear whether prion-free cows would be healthy. The authors’ comprehensive health assessment put this concern to rest, at least for young animals.

Studies to determine whether prion-free cows are resistant to mad cow disease take many years and are currently underway. However, preliminary laboratory tests showed that the animals’ brain tissue blocks the spread of misfolded prion protein, unlike the brain tissue of ordinary cows.

Author contacts:
Yoshimi Kuroiwa (Kirin Brewery Co, Tokyo, Japan and Gemini Science Inc, La Jolla, CA, USA)
Tel: +1 605 361 6793; E-mail: [email protected]

James Robl (Hematech Inc, Sioux Falls, SD, USA)
Tel: +1 605 361 6793; E-mail: [email protected]

Juergen Richt (National Animal Disease Center, USDA, Ames, IA, USA)
Tel: +1 515 663 7366; E-mail: [email protected]

Other papers from Nature Biotechnology to be published online at the same time and with the same embargo:

[2] Computational prediction of proteotypic peptides for quantitative proteomics
DOI: 10.1038/nbt1275

****************************************NATURE GENETICS ***********************

[3], [4] & [5] New breast cancer susceptibility gene identified

DOI: 10.1038/ng1942
DOI: 10.1038/ng1947
DOI: 10.1038/ng1959

Individuals with mutations in a gene called PALB2 have more than twice the normal risk of breast cancer, according to a study to be published in the February issue of Nature Genetics.

The protein encoded by PALB2 was recently shown to interact with and stabilize another protein called BRCA2. As mutations in BRCA2 result in a dramatic increase in risk of breast cancer, Nazneen Rahman and colleagues sequenced PALB2 in approximately 1,000 individuals with familial breast cancer in search of mutations. Mutations were identified in one copy of PALB2 in 10 of these individuals, while no mutations were found in more than 1,000 individuals without breast cancer. Although PALB2 is a relatively small contributor to the overall incidence of breast cancer in the general population, it is now the fourth susceptibility gene to be identified by the strategy of resequencing candidate genes in families where breast cancer is common. This strategy may be applicable to the discovery of genes that confer elevated risk of other cancers as well.

In two related studies, Johan de Winter and colleagues and Rahman and colleagues show that individuals with mutations in both copies of PALB2 have Fanconi anemia, a syndrome characterized by a range of birth defects, bone marrow failure, growth retardation, and cancer predisposition. This is the twelfth gene found with mutations in individuals with Fanconi anemia, and the third (with BRCA2 and BRIP1) that is associated with elevated risk of breast cancer when only one copy is mutated.

Author contacts:
Johan de Winter (VU University Medical Center, Amsterdam, The Netherlands)
Tel: +31 20 4442162; E-mail: [email protected]

Author paper [3]
Nazneen Rahman (Institute of Cancer Research, Sutton, UK)

Author papers [4] & [5]
Please note this author is away at the moment. For all enquiries please contact:

Emma Gilgun-Jones (Press Office, Cancer Research UK, London, UK)
Tel: +44 207 061 8311 or +44 7050 264 059; E-mail: [email protected]

[6] & [7] Evidence for a stem cell origin of cancer

DOI: 10.1038/ng1941
DOI: 10.1038/ng1950

Genes that are reversibly silenced in embryonic stem cells are over-represented among genes that are permanently silenced in cancers, according to two studies to be published in the February issue of Nature Genetics. This link provides support for the hypothesis that cancer arises from small populations of stem cells.

Stem cells maintain their ability to proliferate indefinitely by reversibly silencing genes that promote differentiation. The Polycomb complex of proteins is required for this gene silencing in embryonic stem cells. Peter Laird and colleagues observed that of 177 genes silenced by Polycomb in embryonic stem cells, 77 of these are permanently silenced by chemical modification of DNA (methylation) in colorectal tumours. This is far more than the number expected by chance. The authors suggest that Polycomb silencing of genes in stem cells ‘pre-marks’ them for permanent silencing by DNA methylation, which is often observed in cancer. In an independent study, Howard Cedar and colleagues show that genes that are silenced by DNA methylation in cancer are frequently modified by the Polycomb complex in normal tissues. The authors conclude that the gene silencing associated with cancer ‘locks in’ the reversible silencing that is observed in noncancerous cells or stem cells.

Author contacts:
Peter Laird (University of Southern California, Los Angeles, CA, USA)
Tel: +1 323 865 0650; E-mail: [email protected]

Author paper [6]
Howard Cedar (Hebrew University Medical School, Jerusalem, Israel)
Tel: +972 2 675 8167; E-mail: [email protected]

Author paper [7]

[8] Genetic risk factor for Crohn disease found

DOI: 10.1038/ng1954

A variant of a protein that normally promotes the digestion and clearance of bacteria by cells is associated with elevated risk of Crohn disease, according to a study to be published in the February issue of Nature Genetics.

Crohn disease in an inflammatory bowel disease that tends to run in families and as such is thought to have a significant genetic component. Jochen Hampe and colleagues chose more than 7,000 genetic variants across the genome that are known to alter the sequence of individual proteins, and assessed their frequencies in several hundred individuals from Germany with the disease. They found a variant of the gene encoding the protein ATG16L1 to be significantly more likely to be present in individuals with Crohn disease than in those who did not have the disease. The result was confirmed in a group from the UK, lending credibility to the finding.

The risk conferred by the ATG16L1 variant was also apparent in individuals who are already known to be at extra risk owing to a variant in the gene CARD15, suggesting that the products of these genes might interact. The fact that ATG16L1 is involved in clearance of bacteria is consistent with the idea that Crohn disease results from inappropriate immune responses to foreign substances.

Author contact:
Jochen Hampe (Christian-Albrechts University, Kiel, Germany)
Tel: +49 431 597 1246; E-mail: [email protected]

****************************NATURE IMMUNOLOGY *************************

[9] Tolerating the gut

DOI: 10.1038/ni1427

New research in the February issue of Nature Immunology reveals why the immune system remains in check and does not attack gut tissues despite being full of bacteria.

Previous work revealed microbial compounds are powerful inducers of immune responses, yet this poses a dilemma for the gut. Shannon Turley and colleagues sought to address this question. They identified specific cells found in regional lymph nodes that express proteins previously thought only to be expressed in highly specialized tissues or organs, such as the eye, gut or pancreas. The resident lymph node cells present these tissue-specific proteins to immune cells, thereby rendering them tolerant of and harmless toward the tissues expressing these proteins.

Importantly, these lymph node cells differ from conventional antigen-presenting cells that activate the immune system and are responsive to bacterial products. These findings identify another means by which the body protects itself against autoimmune attack.

Author contact:
Shannon J Turley (Dana Farber Cancer Institute, Boston, MA, USA)
Tel +1 617 632 4990; E-mail: [email protected]

Additional comment on the paper:
Michael J Bevan (University of Washington, Seattle, WA, USA)
Tel +1 206 685 3610; E-mail: [email protected]

Other papers from Nature Immunology to be published online at the same time and with the same embargo:

[10] Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells
DOI: 10.1038/ni1424

Items from other Nature journals to be published online at the same time and with the same embargo:


[11] Selective inhibitors of death in mutant huntingtin cells
DOI: 10.1038/nchembio852


[12] A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14
DOI: 10.1038/nm1528

[13] Anorectic estrogen mimics the effect of leptin on the rewiring of melanocortin cells and Stat3 signaling in obese animals
DOI: 10.1038/nm1525


[14] Spatial relational learning persists following neonatal hippocampal lesions in macaque monkeys
DOI: 10.1038/nn1820

[15] Spatiotopic selectivity of BOLD responses to visual motion in human MT
DOI: 10.1038/nn1824


[16] Nucleotide recognition by the cytoplasmic domain of the human chloride transporter ClC-5
DOI: 10.1038/nsmb1188

[17] The Ndc80/Hec1 complex is a contact point for kinetochore-microtubule attachment
DOI: 10.1038/nsmb1186


[18] Optical induction of synaptic plasticity using a light-sensitive channel
DOI: 10.1038/nmeth988



The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

Buenos Aires: 3

Herston: 6
Parkville: 9
Perth: 15

Innsbruck: 6, 12

Montreal: 4

Jouy-en-Josas: 9
Paris: 3

Berlin: 4, 8
Braunschweig: 12
Dusseldorf: 4
Frankfurt: 13
Freiburg: 12
Hannover: 12
Heidelberg: 2
Jena: 8
Kiel: 8
Saarbrucken: 8
Wuerzburg: 4

Haifa: 7
Jerusalem: 7
Rehovot: 10
Tel Aviv: 7

Florence: 15
Milan: 11, 15
Pisa: 15

Tokyo: 1

Kuala Lumpur: 4

Amsterdam: 3

Basel: 18
Fribourg: 14
Zurich: 2, 16

Ankara: 4

Cambridge: 5
London: 4, 6, 8, 12
Manchester: 5
Southampton: 5
Surrey: 4, 5


Foster City: 8
La Jolla: 1
Los Angeles: 2, 6
Sacramento: 14

New Haven: 13

Indianapolis: 4

Ames: 1

Baltimore: 3
Bethesda: 12

Boston: 3, 9, 10, 17
Charlestown: 11

St Louis: 15

New York
New York: 4, 11, 13

North Carolina
Durham: 11

South Dakota:
Sioux Falls: 1

Galveston: 1
San Antonio: 13

Seattle: 2


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Katherine Anderson (Nature London)
Tel: +44 20 7843 4502; E-mail: [email protected]

Ruth Francis (Senior Press Officer, Nature, London)
Tel: +44 20 7843 4562; E-mail: [email protected]

For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Biotechnology (New York)
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Tel: +1 212 726 9284; E-mail: [email protected]

Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail: [email protected]

Nature Genetics (New York)
Orli Bahcall
Tel: +1 212 726 9311; E-mail: [email protected]

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)
Allison Doerr
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Nature Neuroscience (New York)
Sandra Aamodt (based in California)
Tel: +1 530 795 3256; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)
Michelle Montoya
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Published: 31 Dec 2006

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