(mentions CMT) Foot pad skin biopsy in mouse models of hereditary neuropathy

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Glia. 2010 Sep 27

Foot pad skin biopsy in mouse models of hereditary neuropathy.

Dacci P, Dina G, Cerri F, Previtali SC, ID, Lauria G, Feltri ML, Bolino A,

Comi G, Wrabetz L, Quattrini A.

Department of Neurology, Division of Neuroscience and INSPE, Neuropathology

Unit, Milan, Italy.

Abstract

Numerous transgenic and knockout mouse models of human hereditary neuropathies

have become available over the past decade. We describe a simple, reproducible,

and safe biopsy of mouse skin for histopathological evaluation of the peripheral

nervous system (PNS) in models of hereditary neuropathies.

We compared the diagnostic outcome between sciatic nerve and dermal nerves found

in skin biopsy (SB) from the hind foot. A total of five animal models of

different Charcot-Marie-Tooth neuropathies, and one model of congenital muscular

dystrophy associated neuropathy were examined.

In wild type mice, dermal nerve fibers were readily identified by

immunohistochemistry, light, and electron microscopy and they appeared similar

to myelinated fibers in sciatic nerve. In mutant mice, SB manifested myelin

abnormalities similar to those observed in sciatic nerves, including

hypomyelination, onion bulbs, myelin outfolding, redundant loops, and tomacula.

In many strains, however, SB showed additional abnormalities-fiber loss, dense

neurofilament packing with lower phosphorylation status, and axonal

degeneration-undetected in sciatic nerve, possibly because SB samples distal

nerves.

SB, a reliable technique to investigate peripheral neuropathies in human beings,

is also useful to investigate animal models of hereditary neuropathies. Our data

indicate that SB may reveal distal axonal pathology in mouse models and permits

sequential follow-up of the neuropathy in an individual mouse, thereby reducing

the number of mice necessary to document pathology of the PNS.