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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Senp1tm1.1Eyeh
targeted mutation 1.1, Edward Yeh
MGI:5882691
Summary 4 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
 		Senp1tm1.1Eyeh/Senp1tm1.1Eyeh Not Specified MGI:5883575
cn2
 		Senp1tm1.1Eyeh/Senp1tm1.1Eyeh
Tg(Pdx1-cre)6Tuv/0 		involves: C57BL/6 MGI:5883576
cn3
 		Senp1tm1.1Eyeh/Senp1+
Tg(Pdx1-cre)6Tuv/0 		involves: C57BL/6 MGI:5883577
cn4
 		Senp1tm1.1Eyeh/Senp1tm1.1Eyeh
Tg(Pdx1-cre/Esr1*)#Dam/0 		involves: C57BL/6 MGI:5883578


Genotype
MGI:5883575
cn1
Allelic
Composition		 Senp1tm1.1Eyeh/Senp1tm1.1Eyeh
Genetic
Background		 Not Specified
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Senp1tm1.1Eyeh mutation (0 available); any Senp1 mutation (65 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
endocrine/exocrine glands
abnormal pancreatic beta cell physiology ( J:226392 )
• pancreatic beta cells from Ad-Cre-treated male mice exhibit loss of both the glucose- and NADPH-dependent amplification of insulin exocytosis
• impaired amplification of exocytosis can be rescued by reintroduction of the SENP1 catalytic domain (cSENP1)
decreased insulin secretion ( J:226392 )
• in vitro, islets isolated from male mice infected with adenovirus expressing Cre (Ad-Cre) exhibit an impaired glucose and KCl-induced insulin secretory response in a perifusion assay, as shown by a reduced area under the curve (AUC) relative to control islets infected with Ad-GFP
• however, the insulin content of mutant islets is unchanged

homeostasis/metabolism
decreased insulin secretion ( J:226392 )
• in vitro, islets isolated from male mice infected with adenovirus expressing Cre (Ad-Cre) exhibit an impaired glucose and KCl-induced insulin secretory response in a perifusion assay, as shown by a reduced area under the curve (AUC) relative to control islets infected with Ad-GFP
• however, the insulin content of mutant islets is unchanged




Genotype
MGI:5883576
cn2
Allelic
Composition		 Senp1tm1.1Eyeh/Senp1tm1.1Eyeh
Tg(Pdx1-cre)6Tuv/0
Genetic
Background		 involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Senp1tm1.1Eyeh mutation (0 available); any Senp1 mutation (65 available)
Tg(Pdx1-cre)6Tuv mutation (3 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
homeostasis/metabolism
decreased insulin secretion ( J:226392 )
• in vitro, islets isolated from male mice exhibit an impaired secretory response to glucose (16.7 mM) and KCl (30 mM) in a perifusion assay; the area under the curve (AUC) of the responses to glucose and KCl is reduced
• when KATP channels are held open with diazoxide (100 uM), isolated islets show a blunted secretory response to KCl (30 mM) at 16.7 mM glucose
• impaired insulin secretion is likely due to impaired glucose-dependent amplification of exocytosis
• however, the insulin content of mutant islets is unchanged
decreased circulating insulin level ( J:226392 )
• male mice show a significant reduction in the plasma insulin response to oral glucose relative to control littermates
• however, islet morphology and alpha and beta cell mass is normal at 14 weeks of age
impaired glucose tolerance ( J:226392 )
• male mice are glucose intolerant following an oral glucose challenge at 6 and 12 weeks of age
• however, insulin tolerance is similar to that in control littermates

endocrine/exocrine glands
abnormal pancreatic beta cell physiology ( J:226392 )
• pancreatic beta cells exhibit loss of the glucose-dependent amplification of insulin exocytosis and fail to respond to NADPH and glutathione (GSH), unlike control beta cells
• impaired glucose-dependent amplification of exocytosis can be rescued by reintroduction of the SENP1 catalytic domain (cSENP1) via the patch pipette
• action potential firing is only modestly altered in beta cells, although islet intracellular Ca2+ responses remain largely normal
decreased insulin secretion ( J:226392 )
• in vitro, islets isolated from male mice exhibit an impaired secretory response to glucose (16.7 mM) and KCl (30 mM) in a perifusion assay; the area under the curve (AUC) of the responses to glucose and KCl is reduced
• when KATP channels are held open with diazoxide (100 uM), isolated islets show a blunted secretory response to KCl (30 mM) at 16.7 mM glucose
• impaired insulin secretion is likely due to impaired glucose-dependent amplification of exocytosis
• however, the insulin content of mutant islets is unchanged

nervous system
impaired ability to fire action potentials ( J:226392 )
• action potential firing is only modestly affected in pancreatic beta cells, as shown by a small but significant reduction in action potential height with no significant differences in inter-spike membrane potential
• however, islet intracellular Ca2+ responses remain largely normal

growth/size/body
growth/size/body region phenotype ( J:226392 )
N
• male mice exhibit normal body weight between 6 and 14 weeks of age




Genotype
MGI:5883577
cn3
Allelic
Composition		 Senp1tm1.1Eyeh/Senp1+
Tg(Pdx1-cre)6Tuv/0
Genetic
Background		 involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Senp1tm1.1Eyeh mutation (0 available); any Senp1 mutation (65 available)
Tg(Pdx1-cre)6Tuv mutation (3 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
homeostasis/metabolism
impaired glucose tolerance ( J:226392 )
• male mice show an intermediate phenotype of glucose intolerance following an oral glucose challenge




Genotype
MGI:5883578
cn4
Allelic
Composition		 Senp1tm1.1Eyeh/Senp1tm1.1Eyeh
Tg(Pdx1-cre/Esr1*)#Dam/0
Genetic
Background		 involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Senp1tm1.1Eyeh mutation (0 available); any Senp1 mutation (65 available)
Tg(Pdx1-cre/Esr1*)#Dam mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
homeostasis/metabolism
decreased insulin secretion ( J:226392 )
• in vitro, islets isolated from tamoxifen-treated male mice exhibit an impaired glucose and KCl-induced insulin secretory response in a perifusion assay, also shown as a reduced area under the curve (AUC) of the responses to glucose and KCl
• however, the insulin content of mutant islets is unchanged
impaired glucose tolerance ( J:226392 )
• tamoxifen-treated male mice exhibit an exaggerated glucose excursion in response to an oral glucose challenge
• however, insulin tolerance is similar to that in control littermates

endocrine/exocrine glands
decreased insulin secretion ( J:226392 )
• in vitro, islets isolated from tamoxifen-treated male mice exhibit an impaired glucose and KCl-induced insulin secretory response in a perifusion assay, also shown as a reduced area under the curve (AUC) of the responses to glucose and KCl
• however, the insulin content of mutant islets is unchanged




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Send questions and comments to User Support. 		last database update
04/23/2024
MGI 6.23 		The Jackson Laboratory