Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11

Babaya, Naru; Ueda, Hironori; Noso, Shinsuke; Hiromine, Yoshihisa; Nojima, K.; Itoi-Babaya, Michiko; Kobayashi, Misato; Fujisawa, Tomomi; Ikegami, Hiroshi

doi:10.1155/2013/608923

Cited by 4 publications

(10 citation statements)

References 20 publications

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“…Mice with glycemia greater than 16.7 mmol/l were considered hyperglycemic because the NSY strain is a model of type 2 diabetes; therefore, the ad lib blood glucose level can exceed 11.1 mmol/l. Some of the data from NSY and C3H mice have been previously reported [7, 11] and were reanalyzed in this study.…”

Section: Methodsmentioning

confidence: 99%

“…Nagoya-Shibata-Yasuda (NSY) mice [9], an inbred strain of type 2 diabetes with moderate obesity and fatty liver, were established by selective breeding for glucose intolerance from an outbred colony, Jcl:ICR mice, from which NOD mice were also derived [10]. Both NSY and NOD mice are extremely STZ-sensitive strains [5, 7, 11], which suggests a shared genetic basis in the vulnerability of β -cells between these strains. β -cell fragility may be shared between type 1 and type 2 diabetes [6, 12, 13].…”

Section: Introductionmentioning

confidence: 99%

“…Subsequent studies using consomic C3H-11 NSY and C3H-14 NSY mice in which the entire NSY-Chr11 and NSY-Chr14 were introgressed onto the genetic background of control C3H mice clearly demonstrated that NSY-Chr11 and NSY-Chr14 harbor loci for diabetes [16]. Subsequent studies using consomic C3H-11 NSY mice indicated that NSY-derived Chr11 harbors susceptibility to STZ-induced diabetes [7, 11]. However, the STZ sensitivity of the C3H-11 NSY strain is not as strong as that of the NSY parental strain, which suggests that STZ-induced diabetes is under polygenic control and that genes on chromosomes other than Chr11 also contribute to STZ susceptibility [7, 11].…”

Section: Introductionmentioning

confidence: 99%

“…Subsequent studies using consomic C3H-11 NSY mice indicated that NSY-derived Chr11 harbors susceptibility to STZ-induced diabetes [7, 11]. However, the STZ sensitivity of the C3H-11 NSY strain is not as strong as that of the NSY parental strain, which suggests that STZ-induced diabetes is under polygenic control and that genes on chromosomes other than Chr11 also contribute to STZ susceptibility [7, 11].…”

Section: Introductionmentioning

confidence: 99%

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Verification That Mouse Chromosome 14 Is Responsible for Susceptibility to Streptozotocin in NSY Mice

Babaya

Ueda

Noso

et al. 2018

International Journal of Endocrinology

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Introduction Streptozotocin- (STZ-) induced diabetes is under polygenic control, and the genetic loci for STZ susceptibility are mapped to chromosome (Chr) 11 in Nagoya-Shibata-Yasuda (NSY) mice. In addition to Chr11, other genes on different chromosomes may contribute to STZ susceptibility in NSY mice. The aim of this study was to determine whether NSY-Chr14 contributes to STZ susceptibility and contains the STZ-susceptible region. Materials and Methods A consomic C3H-14NSY strain (R0: homozygous for NSY-derived whole Chr14 on the control C3H background), two congenic strains (R1: the region retained proximal and middle segments of NSY-Chr14 and R2: the region retained a proximal segment of NSY-Chr14), and parental NSY and C3H mice were intraperitoneally injected with a single injection of STZ at a dose of 175 mg/kg body weight at 12 weeks of age. Blood glucose levels and body weights were measured at days 0, 1, 2, 4, 5, 7, 8, and 14 after STZ injection. At day 14 after STZ injection, pancreata were dissected and fixed. Results After STZ injection, blood glucose levels were significantly higher in R0 mice than in C3H mice. However, blood glucose levels in R0 mice were not as severely affected as those in NSY mice. In R1 and R2 mice, blood glucose levels were similar to those in C3H mice and were significantly lower than those in R0 mice. Body weights were decreased in NSY and R0 mice; however, this change was not observed in R1, R2, and C3H mice. Although islet tissues in all strains exhibited degeneration and cellular infiltration, histological changes in NSY and R0 mice were more severe than those in R1, R2, and C3H mice. Conclusions These data demonstrated that NSY-Chr14 was a STZ-susceptible chromosome and that STZ susceptibility was mapped to the distal segment of NSY-Chr14.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Verification That Mouse Chromosome 14 Is Responsible for Susceptibility to Streptozotocin in NSY Mice

Babaya

Ueda

Noso

et al. 2018

International Journal of Endocrinology

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“…Blood glucose level was measured at 0, 15, 30, 45, and 60 min. HOMA-IR, an indicator of insulin resistance, was calculated as previously described [29]. Anatomical phenotypes were studied at 11 weeks of experimental period (15 weeks of age).…”

Section: Phenotypic Analysesmentioning

confidence: 99%

Type 2 diabetes susceptibility genes on mouse chromosome 11 under high sucrose environment

et al. 2020

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Background: Both genetic and environmental factors contribute to type 2 diabetes development. We used consomic mice established from an animal type 2 diabetes model to identify susceptibility genes that contribute to type 2 diabetes development under specific environments. We previously established consomic strains (C3H-Chr 11 NSY and C3H-Chr 14 NSY) that possess diabetogenic Chr 11 or 14 of the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of spontaneous type 2 diabetes, in the genetic background of C3H mice. To search genes contribute to type 2 diabetes under specific environment, we first investigated whether sucrose administration deteriorates type 2 diabetesrelated traits in the consomic strains. We dissected loci on Chr 11 by establishing congenic strains possessing different segments of NSY-derived Chr 11 under sucrose administration. Results: In C3H-Chr 11 NSY mice, sucrose administration for 10 weeks deteriorated hyperglycemia, insulin resistance, and impaired insulin secretion, which is comparable to NSY mice with sucrose. In C3H-Chr 14 NSY mice, sucrose administration induced glucose intolerance, but not insulin resistance and impaired insulin secretion. To dissect the gene(s) existing on Chr 11 for sucrose-induced type 2 diabetes, we constructed four novel congenic strains (R1, R2, R3, and R4) with different segments of NSY-derived Chr 11 in C3H mice. R2 mice showed marked glucose intolerance and impaired insulin secretion comparable to C3H-Chr 11 NSY mice. R3 and R4 mice also showed impaired insulin secretion. R4 mice showed significant decreases in white adipose tissue, which is in the opposite direction from parental C3H-Chr 11 NSY and NSY mice. None of the four congenic strains showed insulin resistance. Conclusions: Genes on mouse Chr 11 could explain glucose intolerance, impaired insulin secretion, insulin resistance in NSY mice under sucrose administration. Congenic mapping with high sucrose environment localized susceptibility genes for type 2 diabetes associated with impaired insulin secretion in the middle segment (26.0-63.4 Mb) of Chr 11. Gene(s) that decrease white adipose tissue were mapped to the distal segment of Chr 11. The identification of diabetogenic gene on Chr 11 in the future study will facilitate precision medicine in type 2 diabetes by controlling specific environments in targeted subjects with susceptible genotypes.

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Novel loci for hyperglycemia identified by QTL mapping of longitudinal phenotypes and congenic analysis

Babaya

Itoi-Babaya²,

Ueda

et al. 2023

Sci Rep

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We previously reported that four hyperglycemia loci are located on three chromosomes in the Nagoya-Shibata-Yasuda (NSY) mouse model, commonly used to study type 2 diabetes. However, we did not search for hyperglycemia loci across all chromosomes. In this study, we performed quantitative trait loci (QTLs) mapping of longitudinal phenotypes from crosses between NSY (hyperglycemic) and C3H (normoglycemic) mice. We identified four new QTLs for hyperglycemia, namely Nidd5nsy, Nidd6nsy, Nidd1c3h, and Nidd2c3h, on Chromosome 1, 4, 10, and 13, respectively. These QTLs were associated with hyperglycemia in young mice and had attenuated effects in older mice. Nidd5nsy and Nidd6nsy were hyperglycemic with NSY alleles, and Nidd1c3h and Nidd2c3h were hyperglycemic with C3H alleles. We further bred Nidd5nsy congenic mice and demonstrated that Nidd5nsy has a strong effect on hyperglycemia when young, accompanied by insulin resistance and visceral fat accumulation. These results showed that the effects of individual QTLs strengthened or weakened with age, and that the sum of the effects of QTLs captured the age-related deterioration of glucose tolerance in individuals. Our results support the importance of longitudinal phenotypes in the genetic analysis of polygenic traits and have implications for the genetic basis and pathogenesis of type 2 diabetes in humans.

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Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11

Cited by 4 publications

References 20 publications

Verification That Mouse Chromosome 14 Is Responsible for Susceptibility to Streptozotocin in NSY Mice

Verification That Mouse Chromosome 14 Is Responsible for Susceptibility to Streptozotocin in NSY Mice

Type 2 diabetes susceptibility genes on mouse chromosome 11 under high sucrose environment

Novel loci for hyperglycemia identified by QTL mapping of longitudinal phenotypes and congenic analysis

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