Sensory nerve degeneration in a mouse model mimicking early manifestations of familial amyloid polyneuropathy due to transthyretin Ala97Ser.

Kan, H-W; Chiang, H; Lin, W-M; Yu, I-S; Lin, S-W; Hsieh, S-T

Sensory nerve degeneration in a mouse model mimicking early manifestations of familial amyloid polyneuropathy due to transthyretin Ala97Ser.

Kan, H-W; Chiang, H; Lin, W-M; Yu, I-S; Lin, S-W; Hsieh, S-T.

Afiliación

Kan HW; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chiang H; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin WM; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yu IS; Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin SW; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Hsieh ST; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Neuropathol Appl Neurobiol ; 44(7): 673-686, 2018 12.

Article en En | MEDLINE | ID: mdl-29423915

RESUMEN

AIMS: Sensory nerve degeneration and consequent abnormal sensations are the earliest and most prevalent manifestations of familial amyloid polyneuropathy (FAP) due to amyloidogenic transthyretin (TTR). FAP is a relentlessly progressive degenerative disease of the peripheral nervous system. However, there is a lack of mouse models to replicate the early neuropathic manifestations of FAP. METHODS: We established human TTR knock-in mice by replacing one allele of the mouse Ttr locus with human wild-type TTR (hTTRwt ) or human TTR with the A97S mutation (hTTRA97S ). Given the late onset of neuropathic manifestations in A97S-FAP, we investigated nerve pathology, physiology, and behavioural tests in these mice at two age points: the adult group (8 - 56 weeks) and the ageing group (> 104 weeks). RESULTS: In the adult group, nerve profiles, neurophysiology and behaviour were similar between hTTRwt and hTTRA97S mice. By contrast, ageing hTTRA97S mice showed small fibre neuropathy with decreased intraepidermal nerve fibre density and behavioural signs of mechanical allodynia. Furthermore, significant reductions in sural nerve myelinated nerve fibre density and sensory nerve action potential amplitudes in these mice indicated degeneration of large sensory fibres. The unaffected motor nerve physiology replicated the early symptoms of FAP patients, that is, sensory nerves were more vulnerable to mutant TTR than motor nerves. CONCLUSIONS: These results demonstrate that the hTTRA97S mouse model develops sensory nerve pathology and corresponding physiology mimicking A97S-FAP and provides a platform to develop new therapies for the early stage of A97S-FAP.

Asunto(s)

Neuropatías Amiloides Familiares/patología; Degeneración Nerviosa/patología; Prealbúmina/genética; Células Receptoras Sensoriales/patología; Neuropatías Amiloides Familiares/genética; Animales; Modelos Animales de Enfermedad; Ratones; Ratones Transgénicos; Degeneración Nerviosa/genética

Palabras clave

Familial amyloid polyneuropathy; Transthyretin; intraepidermal nerve fibre; knock-in mice; nerve conduction studies

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Receptoras Sensoriales / Prealbúmina / Neuropatías Amiloides Familiares / Degeneración Nerviosa Límite: Animals Idioma: En Revista: Neuropathol Appl Neurobiol Año: 2018 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google