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Strain Detail Sheet


Strain Name: JU.Cg-Ay/a/Mmmh

Stock Number: 000221-MU

Other Names:

Gene Details:

Allele Symbol: Ay
Name: nonagouti / yellow
Chromosome: 2
Alteration at locus: Spontaneous Mutation

Genetic Alterations:
The mutation appears to be a DNA structural alteration that disrupts a gene, hnRNP associated with lethal yellow (Raly), 5' to the agouti locus and places the agouti locus under the control of the Raly promotor.

Genotype Determination:

ES Cell Line: Not applicable

Strain Description

Phenotype:
The mutant allele is characterized by yellow color, obesity, and diabetes in heterozygotes. It is prenatal lethal in the homozygous state. Therefore, black offspring will be produced every generation. In mice mutant at the agouti locus, these phenotypes are all reduced if the phenotype of the mouse is more eumelanic than pheomelanic,as is the case when the same mutant allele is backcrossed onto the JU/CtLm (MMRRC:000136) inbred background. The mice are yellow until the first molt, then become umbrous (darker dorsally). After about 6 months of age, this umbrous phenotype is gradually lost.

Mammalian Phenotype Terms:
      assigned by genotype

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

Ay/A
        involves: C57BL/6

Ay/a
        B6.Cg-A/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)
  • skin/coat/nails 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)

Ay/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 and 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 b lood 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 BowmanÕs capsules is thickened
  • abnormal renal glomerulus morphology (MGI Ref ID J:26460)
    • some glomeruli exhibit an accumulation of eosinophilic material in the outer parts of the capillary
    • abnormal mesangial cell (MGI Ref ID J:26460)
      • mesangial matrix is thickened
  • abnormal renal tubule morphology (MGI Ref ID J:26460)
    • basement membrane of tubules is thickened
    • hyaline materials or hyaline cast is present in tubules
    • dilated renal tubules (MGI Ref ID J:26460)
  • increased urine glucose level (MGI Ref ID J:26460)
    • present at all ages tested (5, 10, 16 weeks) and in both sexes

Strain Type: Congenic Spontaneous Mutation

Founder genetic background: old mutant of the mouse fancy

Strain genetic background: JU/CtLm (MMRRC:000136)

Strain Development:
Spontaneous mutation maintained by backcross to wildtype JU/CtLm (MMRRC:000136) mice.

Research Applications

Strain Origin

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)

Colony and Husbandry Information

Appearance

Coat color: Yellow

Other:

Breeding

MMRRC Breeding System: Backcross

Breeding Scheme(s):

Generation: N10+

Overall Breeding Performance: Good for young mice but quickly drops off as mice age. Both males and females quickly become sterile if they become obese.

Reproductive Statistics

Viability and Fertility Female Male
Homozygotes are viable: No No
Homozygotes are fertile: No No
Heterozygotes are fertile: Yes Yes
 
Age Reproductive Decline: 20 weeks 20 weeks

Average litter size: Unknown

Recommended wean age: 4 weeks

Special Considerations

Feed mouse chow that contains 4 percent fat.

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on the resuscitated animals.

Order Request Information

Availability Level:

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution:

Please complete the MMRRC Conditions of Use (COU) and provide it at the time your order is placed. Note: The preceding link is to the COU text only; the COU user form will be provided after order submission.

Fees: *

* Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description
Distribution
Fee/unit (US $)
Units Notes
000221-MU-RESUSLitter recovered from cryo-archive
$2,022.00Non-Profit
$4,109.00For-Profit
Litter Recovered litter1; additional fees for any special requests.
000221-MU-SPERMCryo-preserved spermatozoa
$437.00Non-Profit
$817.00For-Profit
Aliquot Approximate quantity.2
000221-MU-EMBRYOCryo-preserved embryos
$1,038.00Non-Profit
$2,621.00For-Profit
Aliquot Approximate quantity3: 20-40 embryos / aliquot

Control Mice:

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one breedable mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains sufficient material (volume and concentration) for at least two IVF or several artificial inseminations (based on our procedures). The MMRRC makes no guarantee concerning success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the "Request this Strain" button above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (207) 288-6009 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to information.


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Last Modified: June 23, 2010