| Official Name |
C57BLKS/J-Leprdb Nos3tm1Unc |
| Description |
Mice homozygous for the diabetes spontaneous mutation
(Lepr) become identifiably obese around 3 to 4 weeks of
age. Elevations of plasma insulin begin at 10 to 14 days and
of blood sugar at four to eight weeks. Affected mice are
polyphagic, polydipsic, and polyuric. The course of the
disease is markedly influenced by genetic background. On the
C57BL/6 background there is compensatory hyperplasia of the
islet B cells, and continued hyperinsulinemia throughout an
18- to 20-month life span. Wound healing is delayed and
metabolic efficiency is increased. Although normal in body
weight, blood glucose, and plasma insulin, heterozygotes
(Lepr/+) also have increased metabolic efficiency and
can survive a prolonged fast longer than controls.
Experiments involving destruction of the ventromedial
nucleus of the hypothalamus suggest that Leprdb may cause a
defect in the hypothalamus. Steroid sulfotransferase
enzymes, aberrantly expressed in diabetic mice, interact
with the Leprdb mutation as modifiers of gender differences
in obesity-induced diabetes susceptibility.
Mice homozygous for the Nos3 targeted mutation are viable
and fertile. They have elevated blood pressure that is about
20 mmHg higher than that seen in normal wildtype siblings.
They also show a decreased heart rate. Female homozygotes
are smaller in body weight than normal wildtype siblings.
Hyperglycemic-euglycemic clamp studies demonstrate that
homozygotes exhibit insulin resistance at the level of the
liver and peripheral tissues.
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