(CJD/Mad Cow Disease) Detection of prions in muscle tissue (of mice)

[Guest guest]

Date 03:37 Mar 22

Subject PRO/AH> Murine prions, presence in muscle tissue

 

MURINE PRIONS, PRESENCE IN MUSCLE TISSUE

***************************************

A ProMED-mail post

 

Source: New York Times, Tue 19 Mar 2002 [edited]

http://www.nytimes.com/2002/03/19/science/life/19MICE.html

 

 

Detection of prions in mouse muscle tissue

---------

Researchers studying mice have made a discovery that is certain to upset

anyone who loves the rump end of beef but worries about mad cow disease. In

mice, at least, the aberrant proteins that cause the condition seem to

accumulate in muscle tissue, especially the hindquarters. Until now, the

harmful proteins had been seen only in brain or nervous system tissue. The

researchers stress that the finding has been seen only in mice and may not

apply to animals that people eat. But, they say, it is alarming enough to

warrant urgent testing of obviously infected livestock to see if their meat

harbors the aberrant proteins, called prions. Prions cause spongiform

encephalopathies, lethal neurological conditions such as mad cow disease in

cattle, chronic wasting disease in elk and deer, and scrapie in sheep. As

far as anyone knows, only the cattle disease has infected people, who are

believed to have contracted it by eating meat from diseased animals.

 

The United States Department of Agriculture (USDA) is now killing all deer

and elk herds that have been exposed to chronic wasting disease, said Dr

Linda Detwiler, a veterinarian who leads the mad cow disease working group

at the department. The USDA will look into the new finding and do

cooperative studies with scientific laboratories around the world, she

said. As of 4 Mar 2002, 116 people, mostly from Britain, had died or were

dying from the human prion disease, called variant Creutzfeldt-Jakob

disease (vCJD).

 

Until now, scientists have believed that harmful prions are found

exclusively in brain, spinal cord, and lymph tissues of infected animals

and that meat becomes contaminated with them in the rendering and

slaughtering process. To prevent prion diseases from spreading, many

governments ban nervous tissue from entering human and certain animal food

supplies. " The message from this work is that we should not take anything

for granted, " says Dr Giuseppe Legname, an adjunct assistant professor of

neurology, who helped carry out the study at the University of California

at San Francisco (UCSF). It should be possible, he says, to test 50

infected animals from various kinds and breeds of livestock to determine

quickly if deadly prions are found in any of their muscle meats.

 

Cattle continue to suffer mad cow disease in Britain, where the epidemic

began in the early 1980s, although the number of newly diagnosed cases in

animals is falling each year. Meanwhile, the disease is increasing on

mainland Europe, where many cattle ate infected meat and bone meal exported

from Britain in the 1990s. An [unrelated] epidemic of chronic wasting

disease in deer and elk is haunting game farms and hunting grounds in the

United States and Canada.

 

The mouse experiment, being reported today in the Proceedings of the

National Academy of Sciences, USA [see below], was begun more than 5 years

ago in the UCSF laboratory of Dr Stanley Prusiner, who was the first person

to describe prion diseases. Prions are normal proteins found on the surface

of cells throughout the body. Their function is not known. Infectious

prions are produced when normal prions, for unknown reasons, assume a

flattened shape that prevents them from being broken down by the body.

Instead, the abnormal prions accumulate into toxic clumps that somehow

produce lethal holes in brain tissue. Infectious prions can convert healthy

prions into abnormal ones, relentlessly propagating the disease.

 

" Prions we knew could be found in tissues outside the central nervous

system, but it was not clear how they got there, " says Dr Patrick J Bosque,

an assistant professor of neurology at the University of Colorado Health

Sciences Center. It was widely believed that prions were not found in

skeletal muscle. People looked in the early years of the mad cow epidemic,

but the tests available then were extremely time consuming and not very

sensitive. Moreover, researchers may have looked at the wrong muscles, says

Bosque. To find out if prions could replicate in muscle tissue

independently, the scientists created mice that " expressed " or made normal

prions in muscle but nowhere else in the body. Whatever prions do, Dr

Legname says, other proteins must be able to compensate in other tissues

since the animals appear healthy. Scientists also know that normal prions

must be present for the disease to take hold, which in this transgenic

mouse could happen only in muscle.

 

When the mice were injected with abnormal mouse prions, the infection

spread inside muscle, Dr Legname says, but not just any muscle. Infectious

prions seemed to favor the mouse's hind leg and were found there in very

high levels, but the reason is not known. But transgenic mice are not

normal creatures, and the ones used in this experiment were especially

sensitive to prions. They were injected with, rather than fed, the

disease-causing agent. So it is too soon to say whether the findings will

be widely applicable. Dr Legname says it would be prudent to test livestock

known to carry prion diseases. He says the tests used in the laboratory

mice could be adapted for cattle, deer and other animals. Tissue will have

to be injected into other animals to see if the infection crosses between

species, a process that may take years.

 

[byline: Sandra Blakeslee]

 

--

ProMED-mail

<promed

 

[The paper referred to above is entitled: Prions in skeletal muscle, by

Patrick J. Bosque and colleagues. The reference is Proc Natl Acad Sci USA

2002; 99(6): 3812-7 (March 19), and the abstract can be accessed at

<http://www.pnas.org/cgi/content/abstract/99/6/3812>.

 

This paper has great theoretical interest, but its immediate relevance to

the consumption of meat is problematic in the continuing absence of

knowledge of the precise route of transmission of variant Creutzfeldt-Jakob

disease (abbreviated vCJD or CJD (new var.) in ProMED-mail) from infected

cattle to the human population.

 

The authors of the paper summarise their findings as follows: " Considerable

evidence argues that consumption of beef products from cattle infected with

bovine spongiform encephalopathy (BSE) prions causes new variant

Creutzfeldt-Jakob disease. In an effort to prevent new variant

Creutzfeldt-Jakob disease, certain " specified offals, " including neural and

lymphatic tissues, thought to contain high titers of prions have been

excluded from foods destined for human consumption [Phillips NA, Bridgeman

J, Ferguson-Smith M. The BSE inquiry. London: Stationery Office, 2000: vol.

6, pp. 413-51]. Here we report that mouse skeletal muscle can propagate

prions and accumulate substantial titers of these pathogens. We found both

high prion titers and the disease-causing isoform of the prion protein

(PrPSc) in the skeletal muscle of wild-type mice inoculated with either the

Me7 or Rocky Mountain Laboratory strain of murine prions. Particular

muscles accumulated distinct levels of PrPSc, with the highest levels

observed in muscle from the hind limb. To determine whether prions are

produced or merely accumulate intramuscularly, we established transgenic

mice expressing either mouse or Syrian hamster PrP exclusively in muscle.

Inoculating these mice intramuscularly with prions resulted in the

formation of high titers of nascent prions in muscle. In contrast,

inoculating mice in which PrP expression was targeted to hepatocytes

resulted in low prion titers. Our data demonstrate that factors in addition

to the amount of PrP expressed determine the tropism of prions for certain

tissues. That some muscles are intrinsically capable of accumulating

substantial titers of prions is of particular concern. Because significant

dietary exposure to prions might occur through the consumption of meat,

even if it is largely free of neural and lymphatic tissue, a comprehensive

effort to map the distribution of prions in the muscle of infected

livestock is needed. Furthermore, muscle may provide a readily biopsied

tissue from which to diagnose prion disease in asymptomatic animals and

even humans. " - Mod.CP]

...............mpp/cp/pg/sh

 

*##########################################################*

ProMED-mail makes every effort to verify the reports that

are posted, but the accuracy and completeness of the

information, and of any statements or opinions based

thereon, are not guaranteed. The reader assumes all risks in

using information posted or archived by ProMED-mail. ISID

and its associated service providers shall not be held

responsible for errors or omissions or held liable for any

damages incurred as a result of use or reliance upon posted

or archived material.

************************************************************

Visit ProMED-mail's web site at <http://www.promedmail.org>.

Send all items for posting to: promed

(NOT to an individual moderator). If you do not give your

full name and affiliation, it may not be posted. Send

commands to /, get archives, help,

etc. to: majordomo. For assistance from a

human being send mail to: owner-majordomo.

############################################################

############################################################

 

End of message

 

 

 

Inbox

Saved Mail

 

 

 

Session last accessed: 05:28:27 22/03/2002

Session timeout will occur at: 07:28:27 22/03/2002

Copyright 2001 iiNet Limited (ABN 48 068 628 937) .

Contact us Privacy policy