Overview

Also Known As:lethal yellow

Nonagouti; agouti yellow (A^y) is a semidominant spontaneous mutation with homozygotes dying before implantation. Heterozygotes are characterized by obesity, yellow hair pigment, black eyes, elevated malic enzyme in the liver, and susceptibility to several kinds of tumors.

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

A^y

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

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Research Applications

Diabetes and Obesity Research
Dermatology Research
Endocrine Deficiency Research
Research Tools
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Reproductive Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the yellow spontaneous mutation (A^y) die before implantation or shortly thereafter. The time of death and type of abnormality is, in part, determined by the genetic background on which the mutation is placed. Hair pigment in heterozygous mice is yellow, but eyes are black. Heterozygotes usually become obese and infertile after the first few months. Increased adipose tissue mass is due to fat-cell hypertrophy. It has been hypothesized that the obesity results from the observed reduction in hypothalamic norepinephrine and dopamine levels. Insulin resistance and hyperglycemia follow development of hyperinsulinemia in early adulthood, although the degree is less severe than on the KK/UpJ genetic background (Stock No. 002468). Heterozygotes are also more susceptible to several kinds of tumors than normal mice, and their spleen cells cause a significantly lower graft vs. host reaction. The level of malic enzyme in the liver is elevated.

Control Suggestions

a/a from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Diani AR; Sawada GA; Hannah BA; Jodelis KS; Connell MA; Connell CL; Vidmar TJ; Wyse BM. 1987. Analysis of pancreatic islet cells and hormone content in the spontaneously diabetic KKAy mouse by morphometry, immunocytochemistry and radioimmunoassay. Virchows Arch A Pathol Anat Histopathol 412(1):53-61PubMed: 2446417 MGI: J:109946
Robbins LS; Nadeau JH; Johnson KR; Kelly MA; Roselli-Rehfuss L; Baack E; Mountjoy KG; Cone RD. 1993. Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 72(6):827-34PubMed: 8458079 MGI: J:4636

View All References

Genetics

A^y

Allele Symbol: A^y

Allele Name	agouti yellow
Allele Type	Spontaneous
Allele Synonym(s)	A(y); Ay
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
Molecular Note	The A^y 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. A report of recombination between A^y and the a and a^x alleles suggests that A^y was a pseudoallele of the a locus on the proximal side. However, cloning of the agouti locus and molecular analysis of a showed that the coding region of the three alleles is identical.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
- Hyperinsulinemia
- Insulin Resistance
- Type 2 Diabetes (NIDDM)
- Hyperglycemia

Genotype: A^y related

Dermatology Research
- Color and White Spotting Defects
Endocrine Deficiency Research
- Adipose Defects
- Adrenal Cortex Defects
Research Tools
- Reproductive Biology Research
Diabetes and Obesity Research
- Obesity With Diabetes
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency Associated with Other Defects
Internal/Organ Research
- Adipose Defects
- Adrenal Cortex Defects
Reproductive Biology Research
- Endocrine Deficiencies Affecting Gonads
- Fertility Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: A^y/A^y
101-A

cellular phenotype

maternal effect
- there are approximately twice the number of cells, development of a small ectoplacental cone and Reichert's membrane, and disintegration of the decidual epithelium characteristic of an advanced implantation site
- introducing homozygous A^y embryos into the uterus of a wild-type mouse delays embryonic death until after implantation begins

mortality/aging

embryonic lethality at implantation, complete penetrance
- putative homozygous embryos appear as small masses of vacuolated cells in decidual crypts at the time normal embryos are implanting; the abnormal embryo is resorbed within 36 hours
- Background Sensitivity - the genotype of the mother, with or without A^y, determines if a homozygous embryo dies at the initial stage of implantation or after the process begins

embryonic lethality

Genotype: A^y/a
involves: KK

adipose tissue phenotype

increased total body fat amount
- adipose tissue weight increases with age, reaching a maximum at 10 weeks of age

homeostasis/metabolism phenotype

hyperglycemia
- marked hyperglycemia (400-500 mg/dl) develops by 16 weeks of age
- blood glucose levels increase with age in both sexes

impaired glucose tolerance

increased urine glucose level
- present at all ages tested (5, 10, 16 weeks) and in both sexes

insulin resistance
- insulin sensitivity is impaired at 10 weeks and lost by 16 weeks

abnormal lipid homeostasis
- the acetate/glucose ratio is higher than control in young mice
- lipogenesis from acetate is elevated at 5 weeks of age, the enhanced activity is maintained until 16 weeks of age

increased circulating insulin level
- markedly elevated plasma immunoreactive insulin (IRI) level increases with age

renal/urinary system phenotype

abnormal renal glomerulus morphology
- some glomeruli exhibit an accumulation of eosinophilic material in the outer parts of the capillary

abnormal renal tubule morphology
- hyaline materials or hyaline cast is present in tubules
- basement membrane of tubules is thickened

expanded mesangial matrix
- mesangial matrix is thickened

dilated renal tubules

increased renal glomerulus basement membrane thickness
- basement membrane of Bowman's capsules is thickened

renal cast
- hyaline materials or hyaline cast is present in tubules

increased urine glucose level
- present at all ages tested (5, 10, 16 weeks) and in both sexes

endocrine/exocrine gland phenotype

abnormal pancreatic islet morphology
- central cavity formation with occasional red blood cells is observed in islets
- islets are hypertrophic in 10-16 week old mice

degranulated pancreatic beta cells
- degranulated islets are infiltrated with fine glycogen granules
- beta cells are degranulated

growth/size/body region phenotype

increased susceptibility to weight gain
- greater body weight gain occurs in females as compared to black KK controls

The following phenotype relates to a compound genotype created using this strain

Genotype: A^y/A
involves: C57BL/6

homeostasis/metabolism phenotype

increased circulating leptin level
- circulating levels of leptin are over 12-fold higher compared to littermate controls

integument phenotype

yellow coat color
- mice have a yellow coat color

liver/biliary system phenotype

increased liver weight
- female mice have almost a 2-fold gain in weight of the liver

pigmentation phenotype

yellow coat color
- mice have a yellow coat color

adipose tissue phenotype

increased gonadal fat pad weight
- female mice have almost a 7-fold gain in weight of fat pad

increased percent body fat/body weight
- 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
- female mice have almost a 6-fold gain in weight of fat pad

increased brown adipose tissue amount
- female mice have a 6-fold gain in weight of BAT compared to littermate controls

increased inguinal fat pad weight
- female mice have a greater than 6-fold gain in weight of fat pad

behavior/neurological phenotype

increased food intake
- 18 week old mice eat about 1.4 times more food during a 7 day period compared to wild-type controls

hypoactivity
- the locomotor activity of mice is about half that of wild-type mice

growth/size/body region phenotype

increased body length
- female but not male mice have a significant 5% increase in their body length

increased susceptibility to weight gain
- mice gain weight at a greater rate than littermate controls starting at six weeks of age

increased liver weight
- female mice have almost a 2-fold gain in weight of the liver

obese
- by 23 weeks of age, female mice have almost double the weight compared to their wild-type littermate controls

Genotype: A^y/a
B6.Cg-A/J

behavior/neurological phenotype

abnormal food intake
- the stress of isolation, restraint, or ip injection inhibits feeding

integument phenotype

abnormal hair follicle melanogenesis
- 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)

pigmentation phenotype

abnormal hair follicle melanogenesis
- 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)

Phenotype Information

References

Diani AR; Sawada GA; Hannah BA; Jodelis KS; Connell MA; Connell CL; Vidmar TJ; Wyse BM. 1987. Analysis of pancreatic islet cells and hormone content in the spontaneously diabetic KKAy mouse by morphometry, immunocytochemistry and radioimmunoassay. Virchows Arch A Pathol Anat Histopathol 412(1):53-61PubMed: 2446417 MGI: J:109946
Robbins LS; Nadeau JH; Johnson KR; Kelly MA; Roselli-Rehfuss L; Baack E; Mountjoy KG; Cone RD. 1993. Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 72(6):827-34PubMed: 8458079 MGI: J:4636

Additional References

Bouchard G; Johnson D; Carver T; Paigen B; Carey MC. 2002. Cholesterol gallstone formation in overweight mice establishes that obesity per se is not linked directly to cholelithiasis risk. J Lipid Res 43(7):1105-13PubMed: 12091495 MGI: J:88773
Bultman SJ; Klebig ML; Michaud EJ; Sweet HO; Davisson MT; Woychik RP. 1994. Molecular analysis of reverse mutations from nonagouti (a) to black-and-tan (a(t)) and white-bellied agouti (Aw) reveals alternative forms of agouti transcripts. Genes Dev 8(4):481-90PubMed: 8125260 MGI: J:16984
Bultman SJ; Michaud EJ; Woychik RP. 1992. Molecular characterization of the mouse agouti locus. Cell 71(7):1195-204PubMed: 1473152 MGI: J:3523
Chen Y; Duhl DM; Barsh GS. 1996. Opposite orientations of an inverted duplication and allelic variation at the mouse agouti locus. Genetics 144(1):265-77PubMed: 8878692 MGI: J:35710
Duhl DM; Stevens ME; Vrieling H; Saxon PJ; Miller MW; Epstein CJ; Barsh GS. 1994. Pleiotropic effects of the mouse lethal yellow (Ay) mutation explained by deletion of a maternally expressed gene and the simultaneous production of agouti fusion RNAs. Development 120(6):1695-708PubMed: 8050375 MGI: J:18921
Horvath TL; Diano S; Miyamoto S; Barry S; Gatti S; Alberati D; Livak F; Lombardi A; Moreno M; Goglia F; Mor G; Hamilton J; Kachinskas D; Horwitz B; Warden CH. 2003. Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice. Int J Obes Relat Metab Disord 27(4):433-42PubMed: 12664076 MGI: J:82916
Hustad CM; Perry WL; Siracusa LD; Rasberry C; Cobb L; Cattanach BM; Kovatch R; Copeland NG; Jenkins NA. 1995. Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus. Genetics 140(1):255-65PubMed: 7635290 MGI: J:24934
Iwatsuka H; Shino A; Suzuoki Z. 1970. General survey of diabetic features of yellow KK mice. Endocrinol Jpn 17(1):23-35PubMed: 5468422 MGI: J:26460
Klebig ML; Wilkinson JE; Geisler JG; Woychik RP. 1995. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur [see comments] Proc Natl Acad Sci U S A 92(11):4728-32PubMed: 7761391 MGI: J:25738
McPherron AC; Lee SJ. 2002. Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest 109(5):595-601PubMed: 11877467 MGI: J:75344
Michaud EJ; Bultman SJ; Klebig ML; van Vugt MJ; Stubbs LJ; Russell LB; Woychik RP. 1994. A molecular model for the genetic and phenotypic characteristics of the mouse lethal yellow (Ay) mutation. Proc Natl Acad Sci U S A 91(7):2562-6PubMed: 8146154 MGI: J:17512
Michaud EJ; Bultman SJ; Stubbs LJ; Woychik RP. 1993. The embryonic lethality of homozygous lethal yellow mice (Ay/Ay) is associated with the disruption of a novel RNA-binding protein. Genes Dev 7(7A):1203-13PubMed: 8319910 MGI: J:12911
Michaud EJ; van Vugt MJ; Bultman SJ; Sweet HO; Davisson MT; Woychik RP. 1994. Differential expression of a new dominant agouti allele (Aiapy) is correlated with methylation state and is influenced by parental lineage. Genes Dev 8(12):1463-72PubMed: 7926745 MGI: J:18848
Miller MW; Duhl DM; Vrieling H; Cordes SP; Ollmann MM; Winkes BM; Barsh GS. 1993. Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. Genes Dev 7(3):454-67PubMed: 8449404 MGI: J:4186
Odaka H; Shino A; Ikeda H; Matsuo T. 1992. Antiobesity and antidiabetic actions of a new potent disaccharidase inhibitor in genetically obese-diabetic mice, KKA(y). J Nutr Sci Vitaminol (Tokyo) 38(1):27-37PubMed: 1629784 MGI: J:1263
Perry WL; Hustad CM; Swing DA; Jenkins NA; Copeland NG. 1995. A transgenic mouse assay for agouti protein activity. Genetics 140(1):267-74PubMed: 7635291 MGI: J:24932
Shimizu H; Uehara Y; Negishi M; Shimomura Y; Takahashi M; Fukatsu A; Takahashi S; Tanaka Y; Kashima K; Kobayashi I. 1992. Altered monoamine metabolism in the hypothalamus of the genetically obese yellow (Ay/a) mouse. Exp Clin Endocrinol 99(1):45-8PubMed: 1628697 MGI: J:3201
Siracusa LD; Russell LB; Eicher EM; Corrow DJ; Copeland NG; Jenkins NA. 1987. Genetic organization of the agouti region of the mouse. Genetics 117(1):93-100PubMed: 3666442 MGI: J:8877
Takeda S; Elefteriou F; Levasseur R; Liu X; Zhao L; Parker KL; Armstrong D; Ducy P; Karsenty G. 2002. Leptin regulates bone formation via the sympathetic nervous system. Cell 111(3):305-17PubMed: 12419242 MGI: J:79873
Tsuruta Y; Yoshimatsu H; Hidaka S; Kondou S; Okamoto K; Sakata T. 2002. Hyperleptinemia in A(y)/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression. Am J Physiol Endocrinol Metab 282(4):E967-73PubMed: 11882520 MGI: J:75872
Vrieling H; Duhl DM; Millar SE; Miller KA; Barsh GS. 1994. Differences in dorsal and ventral pigmentation result from regional expression of the mouse agouti gene. Proc Natl Acad Sci U S A 91(12):5667-71PubMed: 8202545 MGI: J:18750
Xu B; Goulding EH; Zang K; Cepoi D; Cone RD; Jones KR; Tecott LH; Reichardt LF. 2003. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 6(7):736-42PubMed: 12796784 MGI: J:84073

Additional - A^y related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:A A A Alternate2
- Genotyping resources and troubleshooting
Breeding Considerations

Mice heterozygous for A^ycan be identified phenotypically; see Strain Description. A^y/A^yhomozygotes die embryonically. The weanlings are sometimes small and can be aggressive.
- Additional Breeding and Husbandry Support
Mating System
- heterozygote x C57BL/6J or C57BL/6J x heterozygot
Appearance
- yellow, affected
  Related Genotype: A^y/a
  
  black, unaffected
  Related Genotype: a/a
Citation
When using the lethal yellow mouse strain in a publication, please cite the originating article(s) and include JAX stock #000021 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for A<y>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:lethal yellow

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Additional Information

Selected References

Ay

Allele Symbol: Ay

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Ay related

Mammalian Phenotype Terms by Genotype

Genotype: Ay/Ay101-A

cellular phenotype

mortality/aging

Genotype: Ay/ainvolves: KK

adipose tissue phenotype

homeostasis/metabolism phenotype

renal/urinary system phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

Genotype: Ay/Ainvolves: C57BL/6

homeostasis/metabolism phenotype

integument phenotype

liver/biliary system phenotype

pigmentation phenotype

adipose tissue phenotype

behavior/neurological phenotype

growth/size/body region phenotype

Genotype: Ay/aB6.Cg-A/J

behavior/neurological phenotype

integument phenotype

pigmentation phenotype

Phenotype Information

References

Additional References

Additional - Ay related

Genotyping Protocols

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

A^y

Allele Symbol: A^y

Genotype: A^y related

Genotype: A^y/A^y
101-A

Genotype: A^y/a
involves: KK

Genotype: A^y/A
involves: C57BL/6

Genotype: A^y/a
B6.Cg-A/J

Additional - A^y related