Jump to content
RemedySpot.com

Distinct disease mechanisms in peripheral neuropathies due to altered peripheral

Rate this topic


Guest guest

Recommended Posts

Guest guest

Neurobiol Dis. 2005 Apr;18(3):656-68.

Distinct disease mechanisms in peripheral neuropathies due to altered

peripheral myelin protein 22 gene dosage or a Pmp22 point mutation.

Giambonini-Brugnoli G, Buchstaller J, Sommer L, Suter U, Mantei N.

Institute for Cell Biology, Department of Biology, ETH-Honggerberg,

Swiss Federal Institute of Technology, Schafmattstrasse 18, CH-8093

Zurich, Switzerland.

Point mutations affecting PMP22 can cause hereditary demyelinating

and dysmyelinating peripheral neuropathies. In addition, duplication

and deletion of PMP22 are associated with Charcot-Marie-Tooth disease

Type 1A (CMT1A) and Hereditary Neuropathy with Liability to Pressure

Palsy (HNPP), respectively. This study was designed to elucidate

disease processes caused by misexpression of Pmp22 and, at the same

time, to gain further information on the controversial molecular

function of PMP22. To this end, we took advantage of the unique

resource of a set of various Pmp22 mutant mice to carry out

comparative expression profiling of mutant and wild-type sciatic

nerves. Tissues derived from Pmp22(-/-) ( " knockout " ), Pmp22(tg)

(increased Pmp22 copy number), and Trembler (Tr; point mutation in

Pmp22) mutant mice were analyzed at two developmental stages: (i) at

postnatal day (P)4, when normal myelination has just started and

primary causative defects of the mutations are expected to be

apparent, and (ii) at P60, with the goal of obtaining information on

secondary disease effects. Interestingly, the three Pmp22 mutants

exhibited distinct profiles of gene expression, suggesting different

disease mechanisms. Increased expression of genes involved in cell

cycle regulation and DNA replication is characteristic and specific

for the early stage in Pmp22(-/-) mice, supporting a primary function

of PMP22 in the regulation of Schwann cell proliferation. In the Tr

mutant, a distinguishing feature is the high expression of stress

response genes. Both Tr and Pmp22(tg) mice show strongly reduced

expression of genes important for cholesterol synthesis at P4, a

characteristic that is common to all three mutants at P60. Finally,

we have identified a number of candidate genes that may play

important roles in the disease process or in myelination per se.

Link to comment
Share on other sites

Join the conversation

You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.

Loading...
×
×
  • Create New...