---
title: "NONcNZO10/LtJ and TALLYHO/JngJ Mice as Polygenic Models of Diabetic Peripheral Neuropathy"
id: "pubmed-42698390"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42698390"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42698390/"
doi: "10.1096/fj.202600848R"
published_at: "2026-09-15T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# NONcNZO10/LtJ and TALLYHO/JngJ Mice as Polygenic Models of Diabetic Peripheral Neuropathy
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42698390
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42698390/)
- **DOI:** [10.1096/fj.202600848R](https://doi.org/10.1096%2Ffj.202600848R)
- **Published At:** 2026-09-15T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This study evaluated two polygenic mouse strains, **NONcNZO10/LtJ (RCS10)** and **TALLYHO/JngJ (TH)**, as models of **diabetic peripheral neuropathy (DPN)**. - Both RCS10 and TH mice developed obesity, hyperglycemia, dyslipidemia, and measurable DPN by 24 weeks of age based on nerve conduction velocities and intraepidermal nerve fiber density assessments. - Hyperinsulinemia was present in RCS10 mice but not in TH mice, indicating metabolic heterogeneity between the strains. - Study design: animals were fed a standard diet from 10 weeks and monitored biweekly for body weight and fasting blood glucose; terminal measurements at 24 weeks included HbA1c, plasma insulin, lipids, NCVs, and IENFD. - Compared with monogenic or high-fat diet–induced models, RCS10 and TH displayed metabolic and neuropathic phenotypes considered to more closely resemble human Type 2 diabetes–related neuropathy. - In an interventional arm, RCS10 mice underwent an 8-week **caloric restriction** protocol (60% of standard intake), which improved metabolic parameters and restored large-fiber function as measured by nerve conduction velocities. - Despite functional improvement after calorie restriction, intraepidermal nerve fiber density did not change over the 8-week intervention period. - The authors conclude RCS10 and TH are clinically relevant polygenic models for studying DPN pathogenesis and for preclinical evaluation of targeted therapeutics. - Study metadata: FASEB J. 2026 Sep 15;40(17):e72275. PMID 42698390. PMCID PMC13545661. DOI 10.1096/fj.202600848R. - The authors reported no conflicts of interest.
## Clinical Analysis & Structured Key Points
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more resources ](https://pubmed.ncbi.nlm.nih.gov/42698390/#linkout) Title & authors Abstract Conflict of interest statement Figures References MeSH terms Grants and funding LinkOut - more resources FASEB J Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22FASEB+J%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22FASEB+J%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42698390/) . 2026 Sep 15;40(17):e72275. doi: 10.1096/fj.202600848R. # NONcNZO10/LtJ and TALLY-HO/JngJ Mice as Novel Models of Diabetic Peripheral Neuropathy [Stéphanie A Eid](https://pubmed.ncbi.nlm.nih.gov/?term=Eid+SA&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-2 "Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Faculty of Medicine and Medical Center, Beirut, Lebanon."), [Andrew D Carter](https://pubmed.ncbi.nlm.nih.gov/?term=Carter+AD&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Emily J Koubek](https://pubmed.ncbi.nlm.nih.gov/?term=Koubek+EJ&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [John M Hayes](https://pubmed.ncbi.nlm.nih.gov/?term=Hayes+JM&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Diana M Rigan](https://pubmed.ncbi.nlm.nih.gov/?term=Rigan+DM&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Chloe Kiriluk](https://pubmed.ncbi.nlm.nih.gov/?term=Kiriluk+C&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Crystal M Pacut](https://pubmed.ncbi.nlm.nih.gov/?term=Pacut+CM&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Phillipe D O'Brien](https://pubmed.ncbi.nlm.nih.gov/?term=O%27Brien+PD&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Jihyun Park](https://pubmed.ncbi.nlm.nih.gov/?term=Park+J&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Dae-Gyu Jang](https://pubmed.ncbi.nlm.nih.gov/?term=Jang+DG&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Eva L Feldman](https://pubmed.ncbi.nlm.nih.gov/?term=Feldman+EL&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#full-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.") Affiliations Expand ### Affiliations * 1 Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA. * 2 Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Faculty of Medicine and Medical Center, Beirut, Lebanon. * PMID: **42698390** * PMCID: [ PMC13545661 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13545661/) * DOI: [ 10.1096/fj.202600848R ](https://doi.org/10.1096/fj.202600848r) Item in Clipboard # NONcNZO10/LtJ and TALLY-HO/JngJ Mice as Novel Models of Diabetic Peripheral Neuropathy Stéphanie A Eid et al. FASEB J. 2026. Show details Display options Display options Format Abstract PubMed PMID FASEB J Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22FASEB+J%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22FASEB+J%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42698390/) . 2026 Sep 15;40(17):e72275. doi: 10.1096/fj.202600848R. ### Authors [Stéphanie A Eid](https://pubmed.ncbi.nlm.nih.gov/?term=Eid+SA&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-2 "Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Faculty of Medicine and Medical Center, Beirut, Lebanon."), [Andrew D Carter](https://pubmed.ncbi.nlm.nih.gov/?term=Carter+AD&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Emily J Koubek](https://pubmed.ncbi.nlm.nih.gov/?term=Koubek+EJ&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [John M Hayes](https://pubmed.ncbi.nlm.nih.gov/?term=Hayes+JM&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Diana M Rigan](https://pubmed.ncbi.nlm.nih.gov/?term=Rigan+DM&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Chloe Kiriluk](https://pubmed.ncbi.nlm.nih.gov/?term=Kiriluk+C&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Crystal M Pacut](https://pubmed.ncbi.nlm.nih.gov/?term=Pacut+CM&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Phillipe D O'Brien](https://pubmed.ncbi.nlm.nih.gov/?term=O%27Brien+PD&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Jihyun Park](https://pubmed.ncbi.nlm.nih.gov/?term=Park+J&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Dae-Gyu Jang](https://pubmed.ncbi.nlm.nih.gov/?term=Jang+DG&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA."), [Eva L Feldman](https://pubmed.ncbi.nlm.nih.gov/?term=Feldman+EL&cauthor_id=42698390)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42698390/#short-view-affiliation-1 "Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.") ### Affiliations * 1 Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA. * 2 Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Faculty of Medicine and Medical Center, Beirut, Lebanon. * PMID: **42698390** * PMCID: [ PMC13545661 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13545661/) * DOI: [ 10.1096/fj.202600848R ](https://doi.org/10.1096/fj.202600848r) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Diabetic peripheral neuropathy (DPN), a severe complication of Type 2 diabetes (T2D), is marked by progressive distal-to-proximal axonal degeneration. Although animal models have advanced our understanding of DPN pathogenesis, preclinical successes rarely translate into effective therapies, underscoring the need for models that more faithfully mirror human disease. In this study, we characterized two polygenic mouse strains, NONcNZO10/LtJ (RCS10) and TALLYHO/JngJ (TH), and found that both models developed obesity, hyperglycemia, dyslipidemia, and DPN by 24 weeks of age. However, hyperinsulinemia was observed only in RCS10 mice. Compared to monogenic and high-fat diet-induced models, the metabolic and neuropathic phenotypes of RCS10 and TH more closely resembled those of human DPN. In the second phase of the study, RCS10 mice were subjected to a calorie-restricted diet (60% of standard intake) for 8 weeks, which improved metabolic health and restored large fiber function, although intraepidermal nerve fiber density remained unchanged. Together, these findings identify RCS10 and TH mice as clinically relevant polygenic models for studying DPN pathogenesis and evaluating targeted therapeutic strategies. **Keywords:** NONcNZO10/LtJ; TALLYHO/JngJ; caloric restriction; diabetic peripheral neuropathy; disease models; polygenic. © 2026 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement The authors declare no conflicts of interest. ## Figures [ ![FIGURE 1](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdaa/13545661/d4674e6a51ff/FSB2-40-e72275-g006.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdaa/13545661/367774fd3f23/FSB2-40-e72275-g006.webp) ** FIGURE 1 ** RCS10 and TH mice develop… ** FIGURE 1 ** RCS10 and TH mice develop metabolic dysfunction. (A) Study design for model phenotyping.… **FIGURE 1** RCS10 and TH mice develop metabolic dysfunction. (A) Study design for model phenotyping. Ten‐week‐old NONcNZO10/LtJ (RCS10), C57BL/6J (BL6, control for RCS10), TALLYHO/JngJ (TH) and SWR/J (control for TH) mice were fed a standard diet and monitored until 24 weeks of age. Body weight (BW) and fasting blood glucose (FBG) were measured biweekly. At 24 weeks of age, terminal assessments included BW, FBG, HbA1c, plasma insulin and lipids, as well as diabetic peripheral neuropathy (DPN) phenotyping (nerve conduction velocities and intraepidermal nerve fiber densities). Terminal (B, F) BW, (C, G) FBG, (D, H) HbA1c, and (E, I) insulin in RCS10 and BL6 mice (B–E, _n_ = 6) and TH and SWR/J mice (F, G, _n_ = 6; H, I, _n_ = 9). Each data point represents an individual animal. Data are represented as mean ± standard deviation. Two‐tailed unpaired _t_ ‐test. ns, not significant, *_p_ < 0.05, **_p_ < 0.01, ****_p_ < 0.0001. [ ![FIGURE 2](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdaa/13545661/bab75af6cdbb/FSB2-40-e72275-g005.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdaa/13545661/760a52298b1c/FSB2-40-e72275-g005.webp) ** FIGURE 2 ** RCS10 and TH mice have… ** FIGURE 2 ** RCS10 and TH mice have altered lipid profiles. Terminal (A, E) non‐esterified fatty… **FIGURE 2** RCS10 and TH mice have altered lipid profiles. Terminal (A, E) non‐esterified fatty acid (NEFA), (B, F) cholesterol (CHOL), (C, G) triglyceride (TG), and (D, H) phospholipid (PPL) levels in BL6 and RCS10 mice (A–D, _n_ = 6) and SWR/J and TH mice (E–H, _n_ = 6). Each data point represents an individual animal. Data are represented as mean ± standard deviation. Two‐tailed unpaired _t_ ‐test. ns, not significant, *_p_ < 0.05, **_p_ < 0.01, ****_p_ < 0.0001. [ ![FIGURE 3](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdaa/13545661/68577e1e7a0d/FSB2-40-e72275-g001.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdaa/13545661/5c49e543c79b/FSB2-40-e72275-g001.webp) ** FIGURE 3 ** RCS10 and TH mice develop… ** FIGURE 3 ** RCS10 and TH mice develop DPN. Terminal (A, D) motor nerve conduction velocities… **FIGURE 3** RCS10 and TH mice develop DPN. Terminal (A, D) motor nerve conduction velocities (MNCV), (B, E) sensory nerve conduction velocities (SNCV), and (C, F) intraepidermal nerve fiber densities (IENFD) in BL6 and RCS10 mice (A, B, _n_ = 6; C, BL6, _n_ = 5, RCS10, _n_ = 6) and SWR/J and TH mice (D, E; _n_ = 8; F, _n_ = 3). Each data point represents an individual animal. Data are represented as mean ± standard deviation. Two‐tailed unpaired _t_ ‐test. *_p_ < 0.05, **_p_ < 0.01, ***_p_ < 0.001, ****_p_ < 0.0001. [ ![FIGURE 4](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdaa/13545661/91211167a436/FSB2-40-e72275-g002.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdaa/13545661/a0904ba8cd7c/FSB2-40-e72275-g002.webp) ** FIGURE 4 ** Dietary restriction improves metabolic dysfunction… ** FIGURE 4 ** Dietary restriction improves metabolic dysfunction in RCS10 mice. (A) Study design for dietary… **FIGURE 4** Dietary restriction improves metabolic dysfunction in RCS10 mice. (A) Study design for dietary intervention paradigm. Nine‐week‐old RCS10 and control SWR/J mice were fed a standard diet. At 16 weeks of age, half of the RCS10 mice were switched to a 60% calorie restricted diet. Body weight (BW) and fasting blood glucose (FBG) were recorded biweekly. Baseline glucose tolerance testing (GTT) and diabetic peripheral neuropathy (DPN) phenotyping (nerve conduction velocities [NCVs]) were measured at 16 weeks of age. Terminal GTT, HbA1C, plasma (insulin and lipids), body composition, and DPN phenotyping (NCVs and intraepidermal nerve fiber densities) were assessed at 24 weeks of age. Terminal (B) BW, (C) GTT, (D) FBG, (E) insulin, and (F) triglycerides (TG) in SWR/J (_n_ = 4), RCS10 (_n_ = 7), and RCS10‐CR (_n_ = 7) mice. Each data point represents an individual animal. Data are represented as mean ± standard deviation. Data in (B, D–F) assessed by one‐way ANOVA with Tukey's multiple comparisons and (C) by repeated measures two‐way ANOVA with T
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