Strain Detail Sheet

Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.

A^y/A

        involves: C57BL/6

• adipose tissue phenotype
  • increased brown adipose tissue amount (MGI Ref ID J:131039)
    • female mice have a 6-fold gain in weight of BAT compared to littermate controls
  • increased gonadal fat pad weight (MGI Ref ID J:131039)
    • female mice have almost a 7-fold gain in weight of fat pad
  • increased inguinal fat pad weight (MGI Ref ID J:131039)
    • female mice have a greater than 6-fold gain in weight of fat pad
  • increased percent body fat (MGI Ref ID J:131039)
    • female mice have almost a 4-fold gain in percentage of body fat compared to littermate controls
    • male mice have almost a 1.8-fold gain in percentage of body fat compared to littermate controls
  • increased retroperitoneal fat pad weight (MGI Ref ID J:131039)
    • female mice have almost a 6-fold gain in weight of fat pad
• behavior/neurological phenotype
  • hypoactivity (MGI Ref ID J:131039)
    • the locomotor activity of mice is about half that of wild-type mice
  • increased eating behavior (MGI Ref ID J:131039)
    • 18 week old mice eat about 1.4 times more food during a 7 day period compared to wild-type controls
• growth/size phenotype
  • increased body length (MGI Ref ID J:131039)
    • female but not male mice have a significant 5% increase in their body length
  • increased susceptibility to weight gain (MGI Ref ID J:131039)
    • mice gain weight at a greater rate than littermate controls starting at six weeks of age
  • obese (MGI Ref ID J:131039)
    • by 23 weeks of age, female mice have almost double the weight compared to their wild-type littermate controls
• homeostasis/metabolism phenotype
  • increased circulating leptin level (MGI Ref ID J:131039)
    • circulating levels of leptin are over 12-fold higher compared to littermate controls
• liver/biliary system phenotype
  • increased liver weight (MGI Ref ID J:131039)
    • female mice have almost a 2-fold gain in weight of the liver
• pigmentation phenotype
  • yellow coat color (MGI Ref ID J:131039)
    • mice have a yellow coat color
• integument phenotype
  • yellow coat color (MGI Ref ID J:131039)
    • mice have a yellow coat color

A^y/a

        B6.Cg-A<y>/J

• behavior/neurological phenotype
  • abnormal food intake (MGI Ref ID J:102986)
    • the stress of isolation, restraint, or ip injection inhibits feeding
• pigmentation phenotype
  • abnormal hair follicle melanogenesis (MGI Ref ID J:1295)
    • tyrosinase levels in hairbulb melanocytes ,as determined by 35S methionine incorporation and immunotitration, are reduced in comparison to a/a controls
    • decreased tyrosinase suggests the production of predominantly phaeomelanin (yellow)
• integument phenotype
  • abnormal hair follicle melanogenesis (MGI Ref ID J:1295)
    • tyrosinase levels in hairbulb melanocytes ,as determined by 35S methionine incorporation and immunotitration, are reduced in comparison to a/a controls
    • decreased tyrosinase suggests the production of predominantly phaeomelanin (yellow)

A^y/a

        involves: KK

• homeostasis/metabolism phenotype
  • abnormal lipid homeostasis (MGI Ref ID J:26460)
    • lipogenesis from acetate is elevated at 5 weeks of age, the enhanced activity is maintained until 16 weeks of age
    • the acetate/glucose ratio is higher than control in young mice
  • hyperglycemia (MGI Ref ID J:26460)
    • blood glucose levels increase with age in both sexes
    • marked hyperglycemia (400-500 mg/dl) develops by 16 weeks of age
  • impaired glucose tolerance (MGI Ref ID J:26460)
  • increased circulating insulin level (MGI Ref ID J:26460)
    • markedly elevated plasma immunoreactive insulin (IRI) level increases with age
  • increased urine glucose level (MGI Ref ID J:26460)
    • present at all ages tested (5, 10, 16 weeks) and in both sexes
  • insulin resistance (MGI Ref ID J:26460)
    • insulin sensitivity is impaired at 10 weeks an d lost by 16 weeks
• adipose tissue phenotype
  • increased total body fat amount (MGI Ref ID J:26460)
    • adipose tissue weight increases with age, reaching a maximum at 10 weeks of age
• growth/size phenotype
  • increased susceptibility to weight gain (MGI Ref ID J:26460)
    • greater body weight gain occurs in females as compared to black KK controls
• endocrine/exocrine gland phenotype
  • abnormal pancreatic islet morphology (MGI Ref ID J:26460)
    • islets are hypertrophic in 10-16 week old mice
    • central cavity formation with occasional red blood cells is observed in islets
    • degranulated pancreatic beta cells (MGI Ref ID J:26460)
      • beta cells are degranulated
      • degranulated islets are infiltrated with fine glycogen granules
• renal/urinary system phenotype
  • abnormal renal glomerular capsule (MGI Ref ID J:26460)
    • basement membrane of Bowman

      Founder genetic background: old mutant of the mouse fancy

      Strain genetic background: DBA/2J

      Strain Development: This strain was created by backcrossing the spontaneous mutation from C57BL/6J-A^y/a, that was obtained from JAX, onto DBA/2J.

      Suggested Control Mice:

      • Wildtype littermates
      • DBA/2J

• Pigmentation
• Obesity
• Reproduction

Donor: Dr. M. L. Lamoreux, Texas A&M University

Primary Reference:

• Michaud EJ, Bultman SJ, Klebig ML, van Vugt MJ, Stubbs LJ, Russell LB, Woychik RP. A molecular model for the genetic and phenotypic characteristics of the mouse lethal yellow (Ay) mutation. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2562-6. (Medline: 8146154)
• Lamoreux ML, Wakamatsu K, Ito S. Interaction of major coat color gene functions in mice as studied by chemical analysis of eumelanin and pheomelanin. Pigment Cell Res. 2001 Feb;14(1):23-31. (Medline: 11277491)
• Ollmann MM, Lamoreux ML, Wilson BD, Barsh GS. Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo. Genes Dev. 1998 Feb 1;12(3):316-30. (Medline: 9450927)

Coat color: Dilute yellow

Other:

MMRRC Breeding System: Backcross

Breeding Scheme(s):

• Wildtype Female x Heterozygous Male
• DBA/2J Female x Heterozygous Male
• Heterozygous females are fertile, but resulting pups have a poor survival rate to weaning age. Recommend mating heterozygous males to DBA/2J or wildtype females.

Generation: N10+

Overall Breeding Performance: Poor. It is usually very much easier to obtain viable litters if yellow males are mated with nonyellow females, and if the mice are maintained in more than usually crowded conditions. Trying to mate these as pairs probably would not work. Some of the yellow females never breed. So in rederivation, it will be necessary to provide more than three animals per client.

Viability and Fertility:	Female	Male
Homozygotes are viable:	No	No
Homozygotes are fertile:	No	No
Heterozygotes are fertile:	Yes	Yes
Age Reproductive Decline:	6 months	6 months

Average litter size: 6

Recommended wean age: 5 weeks

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.