Description

Strain Information

Former Names TallyHo/JngJ    (Changed: 15-DEC-04 ) Type Inbred Strain; Additional information on Inbred Strains. Visit our online Nomenclature tutorial. Mating System Sibling x Sibling         (Female x Male)   01-MAR-06 Species laboratory mouse H2 Haplotype s Generation F?+F4pF11 (17-SEP-12) Generation Definitions

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Description
TALLYHO mimics many characteristics of human non-insulin-dependent type 2 diabetes mellitus (NIDDM). Male TALLYHO mice develop hyperglycemia, hyperinsulinemia, hyperlipidemia, moderate obesity, and enlargement of the islets of Langerhans. Onset of hyperglycemia is delayed compared to ob/ob (B6.V-Lep^ob) and db/db (BKS.Cg-m +/+ Lepr^db) mice beginning between 10 and 14 weeks of age. Female mice display moderate hyperinsulinemia, hyperlipidemia, and obesity but do not manifest overt diabetes (i.e. hyperglycemia). Chromosomal mapping identified a major diabetes susceptibility locus on Chromosome 19, designated Tanidd1 for TH-associated NIDDM. Breeding and mapping data suggest Tanidd1 is a single recessively inherited gene primarily responsible for the hyperglycemia phenotype in TALLYHO mice. Tanidd1 interacts with other loci including Tanidd2 on Chromosome 13, Tanidd3 on Chromosome 15, Tabw2 (TallyHo-associated body weight) on Chromosome 7, and Tafat (TallyHo-associated fat pad)(Kim et al., 2001).

Development
The TallyHo strain originated from two outbred Theiler Original mice showing polyuria and glucosuria in the laboratory of Dr. E. Simpson (Harrow, UK). In 1994, Dr. Juergen Naggert established a research colony of mice at The Jackson Laboratory following importation of diabetic male mice and normal females. TallyHo was established by selective inbreeding based on the hyperglycemia phenotype of male mice. Following the seventh inbreeding generation, an intercross/backcross strategy was used for four backcross generations with selection for diabetic males mated to females proven to produce diabetic males. Brother x sister inbreeding was then resumed and the colony is currently seven generations following the four backcrosses (>F7NE4F7). Genetic analyses of TallyHo mice reported in Kim et al., 2001 were begun at the F7 generation prebackcrossing while the physiological analyses were carried out at the F1 and F2 postbackrossing generations. Genome scans at these generations detected no residual heterozygosity in the parental mice used for mapping. Scans were conducted using 92 polymorphic SSLP markers spanning the genome. This strain was donated to The Jackson Laboratory in 2004.

Control Information

	Control
	Please Inquire	SWR/J (Stock No. 000689) is recommended as the "normal" genetically related control for TALLYHO/JngJ mice; the two strains share 86.8% of their genotype and 67.1% of their haplotype based on TALLYHO/JngJ single nucleotide polymorphism (SNP) alignment with Swiss family strains.
Considerations for Choosing Controls

Additional Web Information

Comparison of widely used JAX^® Mice for type 2 diabetes and obesity
JAX^® NOTES, Fall 2001; 483. New Type 2 Diabetes Model Developed.
JAX^® NOTES, Fall 2008; 511. TALLYHO, a new polygenic model of type 2 diabetes

Phenotype

Phenotype Information

View Phenotypic Data

Phenotypic Data

Mouse Phenome Database
Phenotype details on TALLYHO/JngJ
TALLYHO/JngJ response to Rosiglitizone

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

       

• homeostasis/metabolism phenotype
• impaired glucose tolerance
  • males exhibit impaired glucose tolerance by 8 weeks of age as measured by IPGTT   (MGI Ref ID J:114221)
  • females exhibit normal glucose tolerance   (MGI Ref ID J:114221)
• increased circulating cholesterol level
  • at 4 weeks of age, mice of both sexes are hypercholesterolemic compared to C57BL/6J mice   (MGI Ref ID J:114221)
• increased circulating glucose level
  • male plasma glucose levels begin increasing by 8 weeks of age and peak (300-400 mg/dl) at 14 weeks   (MGI Ref ID J:114221)
  • female mice are normoglycemic   (MGI Ref ID J:114221)
• • hyperglycemia
    • only males become hyperglycemic although variability exists between litters   (MGI Ref ID J:114221)
• increased circulating insulin level
  • at 4 weeks of age, mice of both sexes are hyperinsulinemic compared to C57BL/6J mice   (MGI Ref ID J:114221)
  • although female mice maintain stable levels, male plasma insulin levels peak (12 ng/ml) between 8-12 weeks   (MGI Ref ID J:114221)
• increased circulating leptin level
  • at 4 weeks of age, mice of both sexes are hyperleptinemic compared to C57BL/6J mice   (MGI Ref ID J:114221)
• increased circulating triglyceride level
  • at 4 weeks of age, mice of both sexes are hypertriglyceridemic compared to C57BL/6J mice   (MGI Ref ID J:114221)
  • males exhibit a higher triglyceride level than females beginning at 6 weeks; levels remain elevated (>600 mg/dl) to at least 16 weeks of age   (MGI Ref ID J:114221)
• insulin resistance
  • at 8 weeks of age fasting and post-glucose challenge insulin levels are higher in TALLYHO/JngJ males than in C57BL/6J males, however, by 16 weeks total insulin secretion in response to glucose is similar between the two strains   (MGI Ref ID J:114221)
• endocrine/exocrine gland phenotype
• abnormal pancreatic islet morphology
  • islets in 16 week old males exhibit granulation, some vacuolation, scattered apoptotic cells and occasional mild fibrosis   (MGI Ref ID J:114221)
• • enlarged pancreatic islets
    • at 4 weeks of age, mice of both sexes exhibit larger islet size as compared to C57BL/6J mice   (MGI Ref ID J:114221)
• pancreas fibrosis
  • mild fibrosis present in some 16 week old males   (MGI Ref ID J:114221)
• growth/size phenotype
• increased body weight
  • increased body weight as compared to C57BL/6J mice   (MGI Ref ID J:114221)
• muscle phenotype
• abnormal muscle cell glucose uptake
  • glucose uptake in the soleus muscle is reduced in TALLYHO/JngJ males as compared to C57BL/6J males   (MGI Ref ID J:114221)

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Hyperglycemia
      males
Hyperinsulinemia
Type 2 Diabetes (NIDDM)

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tabw2TallyHo/Jng
Allele Name		TALLYHO/Jng
Allele Type		QTL
Strain of Origin		TALLYHO/Jng
Gene Symbol and Name		Tabw2, tally ho associated body weight 2
Chromosome		6
Molecular Note		This allele confers increased body weight and increased plasma glucose compared to C57BL/6J.
Allele Symbol		TabwTallyHo/Jng
Allele Name		TallyHo/Jng
Allele Type		QTL
Strain of Origin		TALLYHO/Jng
Gene Symbol and Name		Tabw, TallyHo associated body weight
Chromosome		7
Molecular Note		This allele confers decreased body weight compared to CAST/Ei and C57BL/6J. [MGI Ref ID J:70227]
Allele Symbol		TafatTallyHo/Jng
Allele Name		TallyHo/Jng
Allele Type		QTL
Strain of Origin		TALLYHO/Jng
Gene Symbol and Name		Tafat, TallyHo associated mesenteric fat pad weight
Chromosome		4
Molecular Note		This allele confers decreased adiposity compared to CAST/Ei and C57BL/6J. [MGI Ref ID J:70227]
Allele Symbol		Tanidd1TallyHo/Jng
Allele Name		TallyHo/Jng
Allele Type		QTL
Strain of Origin		TALLYHO/Jng
Gene Symbol and Name		Tanidd1, TallyHo associated non-insulin dependent diabetes mellitus 1
Chromosome		19
Molecular Note		This allele confers susceptibility to hyperglycemia compared to CAST/Ei and C57BL/6. [MGI Ref ID J:70227]
Allele Symbol		Tanidd2TallyHo/Jng
Allele Name		TallyHo/Jng
Allele Type		QTL
Strain of Origin		TALLYHO/Jng
Gene Symbol and Name		Tanidd2, TallyHo associated non-insulin dependent diabetes mellitus 2
Chromosome		13
Molecular Note		This allele confers susceptibility to hyperglycemia compared to C57BL/6. [MGI Ref ID J:70227]
Allele Symbol		Tanidd3TallyHo/Jng
Allele Name		TallyHo/Jng
Allele Type		QTL
Strain of Origin		TALLYHO/Jng
Gene Symbol and Name		Tanidd3, TallyHo associated non-insulin dependent diabetes mellitus 3
Chromosome		16
Molecular Note		This allele confers susceptibility to hyperglycemia compared to CAST/Ei. [MGI Ref ID J:70227]

Genotyping

Genotyping Information

Inbred mouse strains are maintained through sibling (sister x brother) matings; no genotyping required.

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kim JH; Sen S; Avery CS; Simpson E; Chandler P; Nishina PM; Churchill GA; Naggert JK. 2001. Genetic analysis of a new mouse model for non-insulin-dependent diabetes. Genomics 74(3):273-86. [PubMed: 11414755]  [MGI Ref ID J:70227]

Kim JH; Stewart TP; Soltani-Bejnood M; Wang L; Fortuna JM; Mostafa OA; Moustaid-Moussa N; Shoieb AM; McEntee MF; Wang Y; Bechtel L; Naggert JK. 2006. Phenotypic characterization of polygenic type 2 diabetes in TALLYHO/JngJ mice. J Endocrinol 191(2):437-46. [PubMed: 17088413]  [MGI Ref ID J:114221]

Kim JH; Stewart TP; Zhang W; Kim HY; Nishina PM; Naggert JK. 2005. Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity. Physiol Genomics 22(2):171-81. [PubMed: 15870394]  [MGI Ref ID J:100831]

Wang Y; Nishina PM; Naggert JK. 2009. Degradation of IRS1 leads to impaired glucose uptake in adipose tissue of the type 2 diabetes mouse model TALLYHO/Jng. J Endocrinol 203(1):65-74. [PubMed: 19587264]  [MGI Ref ID J:169581]

Additional References

Sung YY; Lee YS; Jung WH; Kim HY; Cheon HG; Yang SD; Rhee SD. 2005. Glucose intolerance in young TallyHo mice is induced by leptin-mediated inhibition of insulin secretion. Biochem Biophys Res Commun 338(4):1779-87. [PubMed: 16288988]  [MGI Ref ID J:104011]

Tabw2^TallyHo/Jng related

Didion SP; Lynch CM; Faraci FM. 2007. Cerebral vascular dysfunction in TallyHo mice: a new model of Type II diabetes. Am J Physiol Heart Circ Physiol 292(3):H1579-83. [PubMed: 17122191]  [MGI Ref ID J:120285]

Kim JH; Saxton AM. 2012. The TALLYHO Mouse as a Model of Human Type 2 Diabetes. Methods Mol Biol 933:75-87. [PubMed: 22893402]  [MGI Ref ID J:186759]

Won HY; Lee JA; Park ZS; Song JS; Kim HY; Jang SM; Yoo SE; Rhee Y; Hwang ES; Bae MA. 2011. Prominent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice. PLoS One 6(3):e18168. [PubMed: 21464945]  [MGI Ref ID J:171666]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX5

Colony Maintenance

Breeding & Husbandry	This strain is maintained by brother x sister matings. At this stage of inbreeding it is important to continually monitor for overt hyperglycemia in male mice. Publications on TallyHo mice should note the current generation of inbreeding. For TallyHo colonies maintained independent of The Jackson Laboratory (TJL), the generation number is denoted by the generation of the original breeder pairs obtained from TJL followed by the number of generations bred independently (e.g. F7NE4F7+3). Please note, SWR/J (Stock No. 000689) is recommended as the "normal" genetically related control for TALLYHO/JngJ mice; the two strains share 86.8% of their genotype and 67.1% of their haplotype based on TALLYHO/JngJ single nucleotide polymorphism (SNP) alignment with Swiss family strains.
Mating System	Sibling x Sibling         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Please Inquire	SWR/J (Stock No. 000689) is recommended as the "normal" genetically related control for TALLYHO/JngJ mice; the two strains share 86.8% of their genotype and 67.1% of their haplotype based on TALLYHO/JngJ single nucleotide polymorphism (SNP) alignment with Swiss family strains.
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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