A Novel Porcine Model of CLN2 Batten Disease that Recapitulates Patient Phenotypes
© 2022. The American Society for Experimental Neurotherapeutics, Inc..
CLN2 Batten disease is a lysosomal disorder in which pathogenic variants in CLN2 lead to reduced activity in the enzyme tripeptidyl peptidase 1. The disease typically manifests around 2 to 4 years of age with developmental delay, ataxia, seizures, inability to speak and walk, and fatality between 6 and 12 years of age. Multiple Cln2 mouse models exist to better understand the etiology of the disease; however, these models are unable to adequately recapitulate the disease due to differences in anatomy and physiology, limiting their utility for therapeutic testing. Here, we describe a new CLN2R208X/R208X porcine model of CLN2 disease. We present comprehensive characterization showing behavioral, pathological, and visual phenotypes that recapitulate those seen in CLN2 patients. CLN2R208X/R208X miniswine present with gait abnormalities at 6 months of age, ERG waveform declines at 6-9 months, vision loss at 11 months, cognitive declines at 12 months, seizures by 15 months, and early death at 18 months due to failure to thrive. CLN2R208X/R208X miniswine also showed classic storage material accumulation and glial activation in the brain at 6 months, and cortical atrophy at 12 months. Thus, the CLN2R208X/R208X miniswine model is a valuable resource for biomarker discovery and therapeutic development in CLN2 disease.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics - 19(2022), 6 vom: 31. Okt., Seite 1905-1919 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Swier, Vicki J [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 07.12.2022 Date Revised 04.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s13311-022-01296-7 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM346176182 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM346176182 | ||
| 003 | DE-627 | ||
| 005 | 20240204231921.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s13311-022-01296-7 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1280.xml |
| 035 | |a (DE-627)NLM346176182 | ||
| 035 | |a (NLM)36100791 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Swier, Vicki J |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Novel Porcine Model of CLN2 Batten Disease that Recapitulates Patient Phenotypes |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.12.2022 | ||
| 500 | |a Date Revised 04.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The American Society for Experimental Neurotherapeutics, Inc. | ||
| 520 | |a CLN2 Batten disease is a lysosomal disorder in which pathogenic variants in CLN2 lead to reduced activity in the enzyme tripeptidyl peptidase 1. The disease typically manifests around 2 to 4 years of age with developmental delay, ataxia, seizures, inability to speak and walk, and fatality between 6 and 12 years of age. Multiple Cln2 mouse models exist to better understand the etiology of the disease; however, these models are unable to adequately recapitulate the disease due to differences in anatomy and physiology, limiting their utility for therapeutic testing. Here, we describe a new CLN2R208X/R208X porcine model of CLN2 disease. We present comprehensive characterization showing behavioral, pathological, and visual phenotypes that recapitulate those seen in CLN2 patients. CLN2R208X/R208X miniswine present with gait abnormalities at 6 months of age, ERG waveform declines at 6-9 months, vision loss at 11 months, cognitive declines at 12 months, seizures by 15 months, and early death at 18 months due to failure to thrive. CLN2R208X/R208X miniswine also showed classic storage material accumulation and glial activation in the brain at 6 months, and cortical atrophy at 12 months. Thus, the CLN2R208X/R208X miniswine model is a valuable resource for biomarker discovery and therapeutic development in CLN2 disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CLN2 Batten disease | |
| 650 | 4 | |a Cortical atrophy | |
| 650 | 4 | |a Electroretinogram a- and b-waves | |
| 650 | 4 | |a Gait | |
| 650 | 4 | |a Miniswine | |
| 650 | 4 | |a Seizures | |
| 650 | 7 | |a Dipeptidyl-Peptidases and Tripeptidyl-Peptidases |2 NLM | |
| 650 | 7 | |a EC 3.4.14.- |2 NLM | |
| 650 | 7 | |a Aminopeptidases |2 NLM | |
| 650 | 7 | |a EC 3.4.11.- |2 NLM | |
| 650 | 7 | |a Serine Proteases |2 NLM | |
| 650 | 7 | |a EC 3.4.- |2 NLM | |
| 700 | 1 | |a White, Katherine A |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Tyler B |e verfasserin |4 aut | |
| 700 | 1 | |a Sieren, Jessica C |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Hans J |e verfasserin |4 aut | |
| 700 | 1 | |a Knoernschild, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaojun |e verfasserin |4 aut | |
| 700 | 1 | |a Rohret, Frank A |e verfasserin |4 aut | |
| 700 | 1 | |a Rogers, Christopher S |e verfasserin |4 aut | |
| 700 | 1 | |a Pearce, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Brudvig, Jon J |e verfasserin |4 aut | |
| 700 | 1 | |a Weimer, Jill M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics |d 2007 |g 19(2022), 6 vom: 31. Okt., Seite 1905-1919 |w (DE-627)NLM167471872 |x 1878-7479 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2022 |g number:6 |g day:31 |g month:10 |g pages:1905-1919 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s13311-022-01296-7 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2022 |e 6 |b 31 |c 10 |h 1905-1919 | ||