Knockout of the amino acid transporter slc6a19 and autoimmune diabetes incidence in female non-obese diabetic (Nod) mice

Matthew F. Waters; Viviane Delghingaro-Augusto; Kiran Javed; Jane E. Dahlstrom; Gaetan Burgio; Stefan Bröer; Christopher J. Nolan

doi:10.3390/metabo11100665

Knockout of the amino acid transporter slc6a19 and autoimmune diabetes incidence in female non-obese diabetic (Nod) mice

Matthew F. Waters, Viviane Delghingaro-Augusto, Kiran Javed, Jane E. Dahlstrom, Gaetan Burgio, Stefan Bröer, Christopher J. Nolan^*

^*Corresponding author for this work

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4 Citations (Scopus)

Abstract

High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. Slc6a19 gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD.Slc6a19^+/+ and NOD.Slc6a19^−/− mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41–1.42; Mantel-Cox log rank test: p = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD.Slc6a19^+/+ and NOD.Slc6a19^−/− mice, respectively (ratio 1.1, 95% confidence interval 0.6–2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice.

Original language	English
Article number	665
Journal	Metabolites
Volume	11
Issue number	10
DOIs	https://doi.org/10.3390/metabo11100665
Publication status	Published - Oct 2021

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@article{7985c800b1a749e7800eb980d95bc6ee,

title = "Knockout of the amino acid transporter slc6a19 and autoimmune diabetes incidence in female non-obese diabetic (Nod) mice",

abstract = "High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. Slc6a19 gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41–1.42; Mantel-Cox log rank test: p = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (ratio 1.1, 95% confidence interval 0.6–2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice.",

keywords = "Amino acid, Aminoaciduria, Diabetes incidence, Insulitis, Neutral amino acid transporter, Non-obese diabetic mouse, Pancreatic islet, Slc6a19 deficiency, Type 1 diabetes",

author = "Waters, {Matthew F.} and Viviane Delghingaro-Augusto and Kiran Javed and Dahlstrom, {Jane E.} and Gaetan Burgio and Stefan Br{\"o}er and Nolan, {Christopher J.}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = oct,

doi = "10.3390/metabo11100665",

language = "English",

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T1 - Knockout of the amino acid transporter slc6a19 and autoimmune diabetes incidence in female non-obese diabetic (Nod) mice

AU - Waters, Matthew F.

AU - Delghingaro-Augusto, Viviane

AU - Javed, Kiran

AU - Dahlstrom, Jane E.

AU - Burgio, Gaetan

AU - Bröer, Stefan

AU - Nolan, Christopher J.

PY - 2021/10

Y1 - 2021/10

N2 - High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. Slc6a19 gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41–1.42; Mantel-Cox log rank test: p = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (ratio 1.1, 95% confidence interval 0.6–2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice.

AB - High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. Slc6a19 gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41–1.42; Mantel-Cox log rank test: p = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (ratio 1.1, 95% confidence interval 0.6–2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice.

KW - Amino acid

KW - Aminoaciduria

KW - Diabetes incidence

KW - Insulitis

KW - Neutral amino acid transporter

KW - Non-obese diabetic mouse

KW - Pancreatic islet

KW - Slc6a19 deficiency

KW - Type 1 diabetes

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U2 - 10.3390/metabo11100665

DO - 10.3390/metabo11100665

M3 - Article

SN - 2218-1989

VL - 11

JO - Metabolites

JF - Metabolites

IS - 10

M1 - 665

ER -

Knockout of the amino acid transporter slc6a19 and autoimmune diabetes incidence in female non-obese diabetic (Nod) mice

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