Phenotypes Associated with This Genotype

Genotype
MGI:2655772

• Allelic Composition: St3gal5^tm1Rlp/St3gal5^tm1Rlp
• Genetic Background: involves: 129S/SvEv * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

abnormal glucose homeostasis ( J:82723 )

• homozygotes show enhanced phosphorylation of the skeletal muscle insulin receptor after ligand binding and display heightened responses in glucose and insulin tolerance tests

hypoglycemia ( J:82723 )

• under fasting conditions, 6-8 weeks old male homozygotes become hypoglycemic more rapidly than wild-type or heterozygous males

• however, no significant differences are observed in fed blood glucose levels among the three genotypes

improved glucose tolerance ( J:82723 )

• fasted 6-8 weeks old male homozygotes show a more rapid reduction of blood glucose levels than wild-type or heterozygous males at 15, 30, and 60 min after i.p. injection of a glucose solution (2 g per kg of body weight)

• after a 45% high-fat regimen for 10 weeks, male homozygotes are significantly more efficient in reducing their blood glucose to nearly baseline levels, whereas similarly treated wild-type males become glucose intolerant

increased insulin sensitivity ( J:82723 )

• fasted 6-8 weeks old male homozygotes become significantly more hypoglycemic at 15 min after an i.p. insulin injection (0.75 units per kg of body weight) than wild-type or heterozygous males, with no significant differences noted at 30 and 60 min after treatment

• after a 45% high-fat regimen for 10 weeks, male homozygotes exhibit lower insulin levels and are significantly more responsive in a glucose tolerance test than wild-type males, indicating protection from high-fat diet-induced insulin resistance

• euglycemic-hyperinsulinemic clamp studies indicate increased insulin sensitivity both in skeletal muscle and liver

abnormal lipid homeostasis ( J:82723 )

• homozygotes fail to synthesize GM3 ganglioside, a simple and widely distributed glycosphingolipid

• major gangliosides present in the brain of mutant mice lack the inner a2,3-linked sialic acid contributed by GM3 synthase

• major brain gangliosides present in wild-type mice (GM1a, GD1a, GD1b, and GT1b) are not found in mutant mice

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:82723 )

N • homozygotes exhibit normal pancreatic islet morphology relative to wild-type littermates