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Experiment

AnkB mutants old mice

Summary

Data Summary

Investigator	Bennett, Vann
Description	Rare functional variants of ankyrin-B have been implicated in human disease, including hereditary cardiac arrhythmia and type 2 diabetes (T2D). Here, we developed murine models to evaluate the metabolic consequences of these alterations in vivo. Specifically, we generated knockin mice that express either the human ankyrin-B variant R1788W, which is present in 0.3% of North Americans of mixed European descent and is associated with T2D, or L1622I, which is present in 7.5% of African Americans. Young AnkbR1788W/R1788W mice displayed primary pancreatic ß cell insufficiency that was characterized by reduced insulin secretion in response to muscarinic agonists, combined with increased peripheral glucose uptake and concomitantly increased plasma membrane localization of glucose transporter 4 (GLUT4) in skeletal muscle and adipocytes. In contrast, older AnkbR1788W/R1788W and AnkbL1622I/L1622I mice developed increased adiposity, a phenotype that was reproduced in cultured adipocytes, and insulin resistance. GLUT4 trafficking was altered in animals expressing mutant forms of ankyrin-B, and we propose that increased cell surface expression of GLUT4 in skeletal muscle and fatty tissue of AnkbR1788W/R1788W mice leads to the observed age-dependent adiposity. Together, our data suggest that ankyrin-B deficiency results in a metabolic syndrome that combines primary pancreatic ß cell insufficiency with peripheral insulin resistance and is directly relevant to the nearly one million North Americans bearing the R1788W ankyrin-B variant. Applicable research area(s): Diabetes, Obesity, Metabolism
Status	Completed
Public Release	6/28/2018
Data Collected?	Data will not be collected for this catalog item
Animal Age	Measured In: week(s) post-natal (w)
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Data Analysis

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Type	Count
Animals	29
Experimental Conditions	1
Catalog Items	1
Curation Info (# flags)	1
Phenotype Assays	13
Phenotype Measurements	377
Histology Images	0
Publications	0
Phenotypes	1

Animals

Strain Name	Common Name	Females	Males	Unknown
C57BL/6	C57BL/6	0	9	0
B6.129-Ank2^tm2Bnt	Ank2^L1622I	0	11	0
B6.129(C)-Ank2^tm3.1Bnt/J	C57BL/6-Ank2^{R1788W /R1788W}	0	9	0

Animals/Strains

Experimental Factors

	Categorical Values
	Name / Abbreviation	Description
	Experimental Factor: Experimental Group
	Control	This animal belongs to the control group for the experiment.
	Experiment	This animal belongs to experimental group that is homozygous for gene manipulations.

Experimental Factor (Units)
Experimental Group

Experimental Factor Values

Phenotype Assays Add / Edit

Name	Abbreviation
glucose uptake	glucose uptake
average clamp glucose	average clamp glucose
fat body mass	fat body mass
lean body mass	lean body mass
total body weight	total body weight
glucose, basal	glucose, basal
hepatic glucose production, basal	hepatic glucose production, basal
glucose synthesis	glucose synthesis
glucose turnover, whole body	glucose turnover, whole body
glycogen/lipid synthesis, whole body	glycogen/lipid synthesis, whole body
glycolysis, whole body	glycolysis, whole body
glycogen synthesis	glycogen synthesis
glycolysis	glycolysis

No documents found.

Mammalian Phenotype (MP) Terms

MPTermID	MPTermName	Definition	Other Results
MP:0005559	increased circulating glucose level	greater than the normal concentration in the blood of this major monosaccharide of the body; it is an important energy source [MGI:cwg\| RGD:cur]	MMPC Search Results

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