Overview

Also Known As: Tubby

These mice carry a spontaneous mutation at the Tub locus characterized by maturity-onset obesity.

Genetic overview

Genetic Background	Generation
000928 CAST/EiJ

Tub^tub

Allele Type	Gene Symbol	Gene Name
Spontaneous	Tub	tubby bipartite transcription factor

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Research Applications

Sensorineural Research
Diabetes and Obesity Research
Endocrine Deficiency Research
Internal/Organ Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the tubby spontaneous mutation experience maturity-onset obesity. Homozygous mutant mice are recognizable by increased body weight at 3 to 4 months in males and at 4 to 6 months in females. Both sexes are fertile. The increased weight is composed of excess adipose tissue. Blood glucose is normal, but plasma insulin is increased prior to obvious signs of obesity and may rise to 20 times normal by 6 months on the C57BL/6 background. Despite elevated plasma total cholesterol, triglycerides, and high-density lipoprotein cholesterol, homozygous mutant mice do not exhibit atherosclerotic fatty streak blood vessel lesions. Tubby mutant mice also exhibit retinal degeneration, initially believed due to the presence of another mutation which was called rd5, but since demonstrated to be a pleiotropic effect of the Tub^tub mutation (Ohlemiller et al., 1997); the retinal phenotype is moderated by a QTL on Chromosome 11 (Ikeda et al., 2002). Tubby homozygotes additionally exhibit progressive hearing loss. The hearing loss is due to apoptotic degeneration of the organ of Corti and loss of afferent neurons. Quantitative trait locus (QTL) analysis identified a region on Chromosome 2 (designated modifier of tubby hearing 1, moth1) whose wild-type allele protects tubby mice from hearing loss (Ikeda et al., 1999); the gene has been identified as Mtap1a, encoding a microtubule-associated protein (Ikeda et al., 2002). A locus suggestively associated with protection from retinal degeneration maps to the same region of Chromosome 2 (Ikeda et al., 2002). Mice homozygous for a targeted null mutation in the tubby gene (not currently available from The Jackson Laboratory) exhibit a phenotype identical to that conferred by the spontaneous tubby mutation (Stubdal, et al., 2000).

Homozygous mice on the CAST background exhibit a phenotype similar to the published C57BL/6 background, however, they are smaller in size (personal communication).

Selected References

Coleman DL; Eicher EM. 1990. Fat (fat) and tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J Hered 81(6):424-7PubMed: 2250094 MGI: J:10872

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Genetics

Tub^tub

Allele Symbol: Tub^tub

Allele Name	tubby
Allele Type	Spontaneous
Allele Synonym(s)	Tub^tub; tubby
Gene Symbol and Name	Tub, tubby bipartite transcription factor
Gene Synonym(s)	rd5; retinal degeneration 5; rd5; tubby; RDOB; tub; tub
Strain of Origin	C57BL/6J
Chromosome	7
General Note	The phenotype associated with retinal degeneration in the tubby stock was referred to as a separate locus, rd5. rd5 was identified in the tubby stock but absent from the parental C57BL/6J stock. Based on the tight linkage of the two phenotypes and the molecular defect underlying the tub mutation, it seemed likely that tub and rd5 were the same gene. This was further supported by a knockout of the tub gene that recapitulated the retinal degeneration phenotype.
Molecular Note	A donor splice site in the 3' region of the gene is abolished by a G to T transversion resulting in a larger transcript containing the unspliced intron.

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).

obesity

Research Areas By Genotype

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

Genotype: Tub^tub related

Sensorineural Research
- Hearing Defects
- Retinal Degeneration
Diabetes and Obesity Research
- Obesity With Diabetes
  - adult onset
- Hyperinsulinemia
- Type 2 Diabetes (NIDDM)
Endocrine Deficiency Research
- Adipose Defects
- Hypothalamus/Pituitary Defects
- Pancreas Defects
Internal/Organ Research
- Adipose Defects
Neurobiology Research
- Hearing 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: Tub^tub/Tub^tub
B6(AU)-Tub/J

behavior/neurological phenotype

increased food intake
- gradually increase food intake

cardiovascular system phenotype

abnormal retinal vasculature morphology
- arteriolar attenuation, venous dilation by 6 weeks
- severe retinal vessel attenuation and sheathing by 5 months

homeostasis/metabolism phenotype

increased circulating cholesterol level
- males, but not females, show a moderate increase in cholesterol levels

increased circulating insulin level
- gradually increase plasma insulin levels over time

increased circulating triglyceride level
- elevated in both males and females, although levels are higher in males than females

nervous system phenotype

abnormal photoreceptor inner segment morphology
- are attenuated

abnormal photoreceptor outer segment morphology
- composed of membranous whirls arranged in an irregular configuration
- normal organized photoreceptor cell outer segments are not observed at any time

cochlear ganglion degeneration
- at the basal end of the cochlea the osseous spiral lamina is partly empty, indicating loss of the afferent processes of the spiral ganglion cells
- spiral ganglion cell bodies in Rosenthal's canal in the most basal half turn were lost in some cochlea

cochlear hair cell degeneration
- a severely degenerated organ of Corti; no hair cells or supporting cells are identifiable

cochlear inner hair cell degeneration
- apparent by 6 postnatal months

cochlear outer hair cell degeneration
- any reduction in the number of outer hair cells in the apical half of mutant cochlea at 5-6 months of age is modest
- apparent by 6 postnatal months
- only the innermost row of outer hair cells is seen, suggesting a partial loss of outer hair cells

decreased retinal photoreceptor cell number
- no photoreceptors were present by 8 months

photoreceptor outer segment degeneration
- largely degenerated

retinal photoreceptor degeneration
- a progressive loss of the photoreceptors

craniofacial phenotype

abnormal bony labyrinth
- at the basal end of the cochlea the osseous spiral lamina is partly empty, indicating loss of the afferent processes of the spiral ganglion cells

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- focal and diffuse loss of pigment epithelium by 5 months
- granular appearance by 6 weeks

skeleton phenotype

abnormal bony labyrinth
- at the basal end of the cochlea the osseous spiral lamina is partly empty, indicating loss of the afferent processes of the spiral ganglion cells

growth/size/body region phenotype

obese
- slowly develop obesity

vision/eye phenotype

abnormal electroretinogram waveform feature
- the amplitude loss was progressive and the electroretinogram was extinguished by 6 months
- the electroretinogram in homozygous mutant is never normal
- the waves are poorly developed and have reduced amplitudes compared to normal controls in the higher intensity waveforms
- with lower intensity flashes, the electroretinography exhibited lower amplitudes

abnormal photoreceptor inner segment morphology
- are attenuated

abnormal photoreceptor outer segment morphology
- composed of membranous whirls arranged in an irregular configuration
- normal organized photoreceptor cell outer segments are not observed at any time

abnormal retinal neuronal layer morphology
- reduced and disorganized nuclear layer by 3 weeks

abnormal retinal photoreceptor layer morphology
- contains at most one-third of thickness of cell in this layer compared to normal mice

abnormal retinal pigment epithelium morphology
- focal and diffuse loss of pigment epithelium by 5 months
- granular appearance by 6 weeks

abnormal retinal vasculature morphology
- arteriolar attenuation, venous dilation by 6 weeks
- severe retinal vessel attenuation and sheathing by 5 months

decreased retinal photoreceptor cell number
- no photoreceptors were present by 8 months

photoreceptor outer segment degeneration
- largely degenerated

retinal degeneration
- Normal - degenerative changes within the inner retina were not observed during first 15 postnatal weeks
- develop progressive retinal degeneration
- only one to two layers of photoreceptor cell nuclei remained at 15-16 postnatal weeks
- pyknotic photoreceptor cell nuclei are observed throughout the first 15 weeks
- rate of photoreceptor loss was constant and both cone and rod photoreceptor cells are degenerated at equal pace
- the rate of degeneration was similar in both the peripheral and central region

retinal deposits
- patches of pigment deposits by 5 months

retinal outer nuclear layer degeneration
- a progressive loss of outer nuclear layers

retinal photoreceptor degeneration
- a progressive loss of the photoreceptors

hearing/vestibular/ear phenotype

abnormal bony labyrinth
- at the basal end of the cochlea the osseous spiral lamina is partly empty, indicating loss of the afferent processes of the spiral ganglion cells

abnormal ear morphology

abnormal hearing physiology

absent tunnel of Corti

cochlear hair cell degeneration
- a severely degenerated organ of Corti; no hair cells or supporting cells are identifiable

cochlear inner hair cell degeneration
- apparent by 6 postnatal months

cochlear outer hair cell degeneration
- any reduction in the number of outer hair cells in the apical half of mutant cochlea at 5-6 months of age is modest
- apparent by 6 postnatal months
- only the innermost row of outer hair cells is seen, suggesting a partial loss of outer hair cells

degeneration of organ of Corti supporting cells
- a severely degenerated organ of Corti; no hair cells or supporting cells are identifiable
- degeneration of phalangeal and other support cells was also observed

impaired hearing
- progressive hearing loss, so that by 5-6 months of age, virtually deaf at 90-100 dB

increased or absent threshold for auditory brainstem response
- at 7, 9, and 12 weeks of age, homozygous mutant mice exhibited 20- to 30-dB higher ABR thresholds across all stimuli at click, 8 kHz, 16 kHz, and 32 kHz
- some homozygous mutants showed elevated ABR thresholds to clicks and 32-kHz pips at 3 weeks of age

organ of Corti degeneration
- a degeneration of organ of Corti in the basal end of the cochlea
- Normal - apical half of the cochlea are normal with preservation of hair cells, supporting cells, and afferent dendrites
- Normal - neither behavioral nor structural evidence of vestibular abnormalities
- Normal - Rosenthal's canal, is similar in appearance in all turns
- Normal - the features of Reissner's membrane, stria vascularis, and the density of nerve fibers within the modiolus are normal
- the transition from a well organized organ of Corti with at least a partial complement of inner and outer hair cells, to a mass of undifferentiated cells occurred in the lower basal turn

Genotype: Tub^tub/Tub^tub
involves: C57BL/6J

nervous system phenotype

abnormal hypothalamus morphology
- absence of NPY2R in arcuate nucleus cilia; however, overall NPY2R expression levels in the hypothalamus are similar to controls
- defect in neuronal ciliary localization of SSTR3 and MCHR1 in the hippocampus CA1 region

Genotype: Tub^tub/Tub^tub
C57BL/6J-Tub

adipose tissue phenotype

increased total body fat amount
- the increase in weight is due to excess adipose tissue associated with all fat deposits

endocrine/exocrine gland phenotype

enlarged pancreatic islets
- islets of Langerhans are moderately enlarged

growth/size/body region phenotype

obese
- increased body weight first becomes obvious at 3-4 months of age in males and 4-6 months in females

homeostasis/metabolism phenotype

increased circulating insulin level
- Normal - however, blood sugar levels are normal up to 9 months of age, the oldest mice tested
- plasma immunoreactive insulin is increased to 2 times the normal prior to signs of obesity
- plasma insulin concentrations increase gradually through out life

increased liver glycogen level
- liver glycogen is slightly increased

immune system phenotype

abnormal Langerhans cell physiology
- islets of Langerhans show indication of hyperactivity in the later stages

liver/biliary system phenotype

hepatic steatosis
- total liver lipids range from 2-3 times the normal

increased liver glycogen level
- liver glycogen is slightly increased

Genotype: Tub^tub/Tub⁺
involves: AKR/J * B6(Cg)-Tub/J

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - no abnormal ear phenotypes detected

Genotype: Tub^tub/Tub^tub
CAST.B6-Tub/Jng

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - no abnormal ear phenotypes detected

References

Coleman DL; Eicher EM. 1990. Fat (fat) and tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J Hered 81(6):424-7PubMed: 2250094 MGI: J:10872

Additional - Tub^tub related

Technical Support

Contact Technical Support

Genotyping Protocols
- Pyrosequencing:Tub^tub
- Sanger sequencing:Tub^tub-SEQ
- Genotyping resources and troubleshooting
Citation
When using the Tubby mouse strain in a publication, please cite the originating article(s) and include JAX stock #003711 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

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Homozygous, Heterozygous or Wild-type for Tub<tub>, 1 pair minimum

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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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.

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Also Known As: Tubby

Genetic overview

Research Applications

Base Price

Detailed Description

Selected References

Tubtub

Allele Symbol: Tubtub

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 Genotype

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

Genotype: Tubtub related

Mammalian Phenotype Terms by Genotype

Genotype: Tubtub/TubtubB6(AU)-Tub/J

behavior/neurological phenotype

cardiovascular system phenotype

homeostasis/metabolism phenotype

nervous system phenotype

craniofacial phenotype

pigmentation phenotype

skeleton phenotype

growth/size/body region phenotype

vision/eye phenotype

hearing/vestibular/ear phenotype

Genotype: Tubtub/Tubtubinvolves: C57BL/6J

nervous system phenotype

Genotype: Tubtub/TubtubC57BL/6J-Tub

adipose tissue phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

Genotype: Tubtub/Tub+involves: AKR/J * B6(Cg)-Tub/J

mammalian phenotype

Genotype: Tubtub/TubtubCAST.B6-Tub/Jng

mammalian phenotype

References

Additional - Tubtub related

Genotyping Protocols

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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Tub^tub

Allele Symbol: Tub^tub

Genotype: Tub^tub related

Genotype: Tub^tub/Tub^tub
B6(AU)-Tub/J

Genotype: Tub^tub/Tub^tub
involves: C57BL/6J

Genotype: Tub^tub/Tub^tub
C57BL/6J-Tub

Genotype: Tub^tub/Tub⁺
involves: AKR/J * B6(Cg)-Tub/J

Genotype: Tub^tub/Tub^tub
CAST.B6-Tub/Jng

Additional - Tub^tub related