KK-Ay Mice: A Model of Obesity and Type 2 Diabetes

2024/03/22

Introduction

CLEA Japan offers the KK-Ay mouse, a model of obesity type 2 diabetes that develops nephropathy when fed a high-sucrose/high-fat diet.

Features

KK mice express rather moderate obesity and hyperglycemia by polygenic inheritance. Since blood glucose levels are increased when the body weight exceeds 35 to 40 g, it appears the body fat accumulation (obesity) plays the most important role in the onset of diabetes. The symptoms are more marked in males and are mild in females.

The Ay gene is the dominant gene of the agouti locus located on chromosome 2. The homozygote (Ay/Ay) is lethal and the heterozygote (Ay/+) causes a yellow coat, obesity, diabetes and hyperinsulinemia 2). KK-Ay mice produced by transfection of KK mice with the Ay gene express severe obesity and hyperglycemia at an early age (7 to 8 weeks after birth). The females have the same symptoms with especially marked obesity and show a higher body weight than males at about 8 weeks of age. Since KK-Ay mice have a yellow coat, they are called yellow KK mice. Because the KK-Ay mouse has dynamic diabetes symptoms from an early stage, they are ideal for screening of antidiabetic drugs and studies on the elucidation of complications.

Points to consider in rearing and experiments

Adequate preliminary rearing

All animals are subject to stress during transport, and blood glucose levels may drop due to overcrowding, insufficient food and water and physical stress during transport. Use these mice in experiments after preliminary rearing for 3 to 5 days to accustom them to their environment.

Individual rearing

Since KK-Ay mice sometimes do not show increases in blood glucose levels when reared in groups, rear them for at least one week individually. When they have to be reared in groups due to spatial limitations, use them in experiments after individual acclimatization for several days.

Large amounts of bedding and high replacement frequency

When the animals have diabetes, pollakiuria occurs, the bedding easily becomes soiled and the external genitalia of males are not clean. Male KK-Ay mice (from 8 weeks of age) are susceptible to abscesses in the external genitalia, probably caused by the soiled bedding. Therefore, replace the bedding with clean bedding in larger amounts and more frequently than with ordinary mice.

Fixed measurement method for blood glucose

Since blood glucose varies due to feeding and measurement methods and the type of samples (blood, serum and plasma), use a fixed method for measurements. Because changes occur when the animals are feeding or fasting, it is necessary to collect blood at a fixed time (about 9 to 10 a.m.) except in special cases and to perform glucose loading after fasting.

Body weight curves

Blood glucose level

Urinary glucose positive rate

Blood chemistry

Hematology

Background

The KK-Ay mouse was produced by Nishimura et al.1) of Nagoya University in 1969 by inserting the Ay gene into the KK mouse as a model of type 2 diabetes that expresses obesity and hyperglycemia earlier and more severely than the KK mouse. The KK mouse originated from individual mice with obesity and hyperglycemia found in 1962 in the K-line of albino mice with a spontaneous crooked tail among mice from the Kasukabe region (K group) by Nakamura, Kondo et al. of Nagoya University and was reared as an animal model of type 2 diabetes. CLEA Japan, Inc. introduced these mice from Nagoya University via Takeda Chemical Industries, Ltd. in 1990 and started to supply them.

Maintenance and production method

Since female KK-Ay mice can not reproduce, the strain is reproduced by mating a female KK mouse with a male KK-Ay mouse. This mating results in albino, black coat or yellow coat individuals. The mice with the yellow coat are selected as KK-Ay mice.

The mice are given autoclaved (121 ℃ , 30 min) sterile CE-2 diet and chlorinated water (4 to 6 ppm) ad libitum.

References

1) Nishimura, M. 1969. Breeding of Mice Strains for Diabetes Mellitus. Exp. Animals 18(4):147-157.
https://pubmed.ncbi.nlm.nih.gov/6995140/

2) Iwatsuka, H., A. Shino, and Z. Suzuoki. 1970. General Survey of Diabetic Features of Yellow KK Mice. Endocrinol. Jpn. 17(1):23-35.
https://pubmed.ncbi.nlm.nih.gov/5468422/

FAQ

Animal care tips.

KK-Ay has a strong fighting tendency, please care the males as single housing after 7 weeks of age.

Characterization of blood glucose level.

Male animals increase blood glucose level rapidly, but female animals are moderate.

Inquiry

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