title: Foot pad skin biopsy in mouse models of hereditary neuropathy.
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.
authors.affiliation: Department of Neurology, Division of Neuroscience and INSPE, Neuropathology Unit, Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dacci
authors.forename: Giorgia
authors.initials: G
authors.lastname: Dina
authors.forename: Federica
authors.initials: F
authors.lastname: Cerri
authors.forename: Stefano Carlo
authors.initials: SC
authors.lastname: Previtali
authors.forename: Ignazio Diego
authors.initials: ID
authors.lastname: Lopez
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Feltri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bolino
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D001706:Biopsy / Q000379:methods*; D002607:Charcot-Marie-Tooth Disease / Q000473:pathology*; D020405:Dermis / Q000294:innervation / Q000473:pathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000294:innervation / Q000473:pathology; D005528:Foot / Q000294:innervation* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D009186:Myelin Sheath / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D012584:Sciatic Nerve / Q000473:pathology; D013497:Sural Nerve / Q000473:pathology