5.08.2006

Lamins are cool!!!

Lamin A-Dependent Nuclear Defects in Human Aging

Paola Scaffidi 1 and
Tom Misteli 1*
Published online April 27 2006; 10.1126/science.1127168 (Science Express Reports)

Lamins are intermediate filament proteins and are the main component of the nuclear lamina. Although these proteins are expressed in different tissues, mutations in the LMN gene that encodes Lamin A and Lamin C, are associated with distinct genetic disorders such as muscular dystrophies, lypodystrophies and progerias.

Now it was found that the same mutation on lamin A protein associated with progeria, a rare disease were children suffer from premature aging, also accumulates in elderly human cells. This mutation originates a truncated version of lamin A.

Two key findings are reported:
- Traces of this truncated version are also observed in cells from young humans, although the protein does not accumulate, as observed in elderly human cells. This suggests that younger cells have mechanisms to destroy this truncated version.
- Cell nuclei from elderly humans have the same morphology and DNA-damage levels as cell nuclei from progeria patients. Impressively, this morphology is reversed when the production of the truncated protein is prevented, by expression of a morpholino targeting the "truncated mRNA".

Maybe in the future cell aging can be prevented by inhibiting the formation of truncated lamin A.... It will be cool to generate a trangenic mice expressing the morpholino that inhibits the formation of spontaneous truncated lamin A.

4 Comments:

At Wednesday, May 10, 2006, Blogger Claudi said...

this is an interesting paper. Two questions, why does the mutation cause premature aging? Does the truncated form mean lack or gain of function?

A more basic question what is a morpholino?

 
At Wednesday, May 10, 2006, Anonymous evil gomez said...

For the first two questions, the answer is unknow. Although some speculation can be made. Lamin is involved in regulation of gene expression. maybe the truncated version either activates or inhibits expression of certain genes related with aging.
Hutchinson-Gilford progeria syndrome is an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

regarding the basic question, morpholinos act like antisense, although they are not made of DNA. They are highly used in zebrafish and Xenopus since RNAi technology is not working yet in these organism. you can find a good description of morpholinos

 
At Wednesday, May 10, 2006, Anonymous Anonymous said...

This comment has been removed by a blog administrator.

 
At Wednesday, December 06, 2006, Anonymous Jon D. Moulton said...

While you cannot express a Morpholino in a transgenic, they do a good job of transient knockdowns. For descriptions of Morpholinos, see:

www.gene-tools.com
http://en.wikipedia.org/wiki/Morpholino
http://blog.myspace.com/127542408

Regards,

- Jon
Gene Tools, LLC

 

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