Strain-based and sex-biased differences in adrenal and pancreatic gene expression between KK/HlJ and C57BL/6 J mice
Abstract Background The ever-increasing prevalence of diabetes and associated comorbidities serves to highlight the necessity of biologically relevant small-animal models to investigate its etiology, pathology and treatment. Although the C57BL/6 J model is amongst the most widely used mouse model du...
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-021-07495-4 |
| _version_ | 1818370200999821312 |
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| author | Angela Inglis Rosario Ubungen Sarah Farooq Princess Mata Jennifer Thiam Soad Saleh Sherin Shibin Futwan A. Al-Mohanna Kate S. Collison |
| author_facet | Angela Inglis Rosario Ubungen Sarah Farooq Princess Mata Jennifer Thiam Soad Saleh Sherin Shibin Futwan A. Al-Mohanna Kate S. Collison |
| author_sort | Angela Inglis |
| collection | DOAJ |
| description | Abstract Background The ever-increasing prevalence of diabetes and associated comorbidities serves to highlight the necessity of biologically relevant small-animal models to investigate its etiology, pathology and treatment. Although the C57BL/6 J model is amongst the most widely used mouse model due to its susceptibility to diet-induced obesity (DIO), there are a number of limitations namely [1] that unambiguous fasting hyperglycemia can only be achieved via dietary manipulation and/or chemical ablation of the pancreatic beta cells. [2] Heterogeneity in the obesogenic effects of hypercaloric feeding has been noted, together with sex-dependent differences, with males being more responsive. The KK mouse strain has been used to study aspects of the metabolic syndrome and prediabetes. We recently conducted a study which characterized the differences in male and female glucocentric parameters between the KK/HlJ and C57BL/6 J strains as well as diabetes-related behavioral differences (Inglis et al. 2019). In the present study, we further characterize these models by examining strain- and sex-dependent differences in pancreatic and adrenal gene expression using Affymetrix microarray together with endocrine-associated serum analysis. Results In addition to strain-associated differences in insulin tolerance, we found significant elevations in KK/HlJ mouse serum leptin, insulin and aldosterone. Additionally, glucagon and corticosterone were elevated in female mice of both strains. Using 2-factor ANOVA and a significance level set at 0.05, we identified 10,269 pancreatic and 10,338 adrenal genes with an intensity cut-off of ≥2.0 for all 4 experimental groups. In the pancreas, gene expression upregulated in the KK/HlJ strain related to increased insulin secretory granule biofunction and pancreatic hyperplasia, whereas ontology of upregulated adrenal differentially expressed genes (DEGs) related to cell signaling and neurotransmission. We established a network of functionally related DEGs commonly upregulated in both endocrine tissues of KK/HlJ mice which included the genes coding for endocrine secretory vesicle biogenesis and regulation: PCSK2, PCSK1N, SCG5, PTPRN, CHGB and APLP1. We also identified genes with sex-biased expression common to both strains and tissues including the paternally expressed imprint gene neuronatin. Conclusion Our novel results have further characterized the commonalities and diversities of pancreatic and adrenal gene expression between the KK/HlJ and C57BL/6 J strains as well as differences in serum markers of endocrine physiology. |
| first_indexed | 2024-12-13T23:35:58Z |
| format | Article |
| id | doaj.art-30e354ae34004166be3b788df7c73e40 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-13T23:35:58Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-30e354ae34004166be3b788df7c73e402022-12-21T23:27:18ZengBMCBMC Genomics1471-21642021-03-0122112610.1186/s12864-021-07495-4Strain-based and sex-biased differences in adrenal and pancreatic gene expression between KK/HlJ and C57BL/6 J miceAngela Inglis0Rosario Ubungen1Sarah Farooq2Princess Mata3Jennifer Thiam4Soad Saleh5Sherin Shibin6Futwan A. Al-Mohanna7Kate S. Collison8Department of Cell Biology, King Faisal Specialist Hospital & Research CentreDepartment of Cell Biology, King Faisal Specialist Hospital & Research CentreDepartment of Cell Biology, King Faisal Specialist Hospital & Research CentreDepartment of Cell Biology, King Faisal Specialist Hospital & Research CentreDepartment of Cell Biology, King Faisal Specialist Hospital & Research CentreDepartment of Cell Biology, King Faisal Specialist Hospital & Research CentreDepartment of Cell Biology, King Faisal Specialist Hospital & Research CentreDepartment of Cell Biology, King Faisal Specialist Hospital & Research CentreDepartment of Cell Biology, King Faisal Specialist Hospital & Research CentreAbstract Background The ever-increasing prevalence of diabetes and associated comorbidities serves to highlight the necessity of biologically relevant small-animal models to investigate its etiology, pathology and treatment. Although the C57BL/6 J model is amongst the most widely used mouse model due to its susceptibility to diet-induced obesity (DIO), there are a number of limitations namely [1] that unambiguous fasting hyperglycemia can only be achieved via dietary manipulation and/or chemical ablation of the pancreatic beta cells. [2] Heterogeneity in the obesogenic effects of hypercaloric feeding has been noted, together with sex-dependent differences, with males being more responsive. The KK mouse strain has been used to study aspects of the metabolic syndrome and prediabetes. We recently conducted a study which characterized the differences in male and female glucocentric parameters between the KK/HlJ and C57BL/6 J strains as well as diabetes-related behavioral differences (Inglis et al. 2019). In the present study, we further characterize these models by examining strain- and sex-dependent differences in pancreatic and adrenal gene expression using Affymetrix microarray together with endocrine-associated serum analysis. Results In addition to strain-associated differences in insulin tolerance, we found significant elevations in KK/HlJ mouse serum leptin, insulin and aldosterone. Additionally, glucagon and corticosterone were elevated in female mice of both strains. Using 2-factor ANOVA and a significance level set at 0.05, we identified 10,269 pancreatic and 10,338 adrenal genes with an intensity cut-off of ≥2.0 for all 4 experimental groups. In the pancreas, gene expression upregulated in the KK/HlJ strain related to increased insulin secretory granule biofunction and pancreatic hyperplasia, whereas ontology of upregulated adrenal differentially expressed genes (DEGs) related to cell signaling and neurotransmission. We established a network of functionally related DEGs commonly upregulated in both endocrine tissues of KK/HlJ mice which included the genes coding for endocrine secretory vesicle biogenesis and regulation: PCSK2, PCSK1N, SCG5, PTPRN, CHGB and APLP1. We also identified genes with sex-biased expression common to both strains and tissues including the paternally expressed imprint gene neuronatin. Conclusion Our novel results have further characterized the commonalities and diversities of pancreatic and adrenal gene expression between the KK/HlJ and C57BL/6 J strains as well as differences in serum markers of endocrine physiology.https://doi.org/10.1186/s12864-021-07495-4MicroarrayStrainGene expressionGlucose homeostasisInsulin tolerance testC57BL/6 J |
| spellingShingle | Angela Inglis Rosario Ubungen Sarah Farooq Princess Mata Jennifer Thiam Soad Saleh Sherin Shibin Futwan A. Al-Mohanna Kate S. Collison Strain-based and sex-biased differences in adrenal and pancreatic gene expression between KK/HlJ and C57BL/6 J mice BMC Genomics Microarray Strain Gene expression Glucose homeostasis Insulin tolerance test C57BL/6 J |
| title | Strain-based and sex-biased differences in adrenal and pancreatic gene expression between KK/HlJ and C57BL/6 J mice |
| title_full | Strain-based and sex-biased differences in adrenal and pancreatic gene expression between KK/HlJ and C57BL/6 J mice |
| title_fullStr | Strain-based and sex-biased differences in adrenal and pancreatic gene expression between KK/HlJ and C57BL/6 J mice |
| title_full_unstemmed | Strain-based and sex-biased differences in adrenal and pancreatic gene expression between KK/HlJ and C57BL/6 J mice |
| title_short | Strain-based and sex-biased differences in adrenal and pancreatic gene expression between KK/HlJ and C57BL/6 J mice |
| title_sort | strain based and sex biased differences in adrenal and pancreatic gene expression between kk hlj and c57bl 6 j mice |
| topic | Microarray Strain Gene expression Glucose homeostasis Insulin tolerance test C57BL/6 J |
| url | https://doi.org/10.1186/s12864-021-07495-4 |
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