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Strain Name:

B6(Cg)-Tubtub/J

Stock Number:

000562

Availability:

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General Terms and Conditions

Former Name      B6.Cg-Tubtub/J    (Changed: 02-FEB-07 )
      B6.Cg-Hbbp +/Hbbs Tubtub/J    (Changed: 31-MAR-05 )
      C57BL/6J-Hbbp +/Hbbs tub    (Changed: 15-DEC-04 )
      C57BL/6J-tub/+    (Changed: 15-DEC-04 )
Genes & Alleles   Hbb;   Hbbs;   Tub;   Tubtub;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Spontaneous Mutation
Specieslaboratory mouse
H2 Haplotypeb

Appearance
black, lean, normal vision
Related Genotype: a/a Tubtub/+

black, fat, retinal degeneration
Related Genotype: a/a Tubtub/Tubtub

Important Note
This strain may be segregating for the Oca2p and s alleles of Hbb.

Strain 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. 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 Tubtub 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).

Strain Development
The Tubtub mutation arose spontaneously in 1977 in The Jackson Laboratory Animal Resources colony of C57BL/6J which was then at F125. After initial maintenance on the C57BL/6J background, a C57BL/6J-Tubtub homozygous male was bred with a female congenic B6.AU-Hbbp and the Hbbp +/Hbbs Tubtub offspring were sibling mated. The colony was maintained by breeding siblings Hbbp +/Hbbs Tubtub x Hbbp +/Hbbs Tubtub or vice versa for many years and in 2002 reached F87. In 2004 isozyme testing for Hbb alleles was replace with PCR testing for the Tubtub allele and the colony reached F90. (Coleman et al., 1978; Coleman and Eicher, 1990.)

Mammalian Phenotype Terms assigned by genotype

Tubtub/Tubtub

        B6(Cg)-Tubtub/J
  • growth/size phenotype
  • obese (MGI Ref ID J:32415)
    • slowly develop obesity
  • behavior/neurological phenotype
  • increased eating behavior (MGI Ref ID J:32415)
    • gradually increase food intake
  • homeostasis/metabolism phenotype
  • increased circulating cholesterol level (MGI Ref ID J:18161)
    • males, but not females, show a moderate increase in cholesterol levels
  • increased circulating insulin level (MGI Ref ID J:32415)
    • gradually increase plasma insulin levels over time
  • increased circulating triglyceride level (MGI Ref ID J:18161)
    • elevated in both males and females, although levels are higher in males than females
  • vision/eye phenotype
  • abnormal eye electrophysiology (MGI Ref ID J:121993)
    • 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
    • the amplitude loss was progressive and the electroretinogram was extinguished by 6 months
  • abnormal retinal neuronal layer morphology (MGI Ref ID J:121993)
    • reduced and disorganized nuclear layer by 3 weeks
    • abnormal retinal photoreceptor layer (MGI Ref ID J:26067)
      • contains at most one-third of thickness of cell in this layer compared to normal mice
      • abnormal photoreceptor inner segment morphology (MGI Ref ID J:26067)
        • are attenuated
      • abnormal photoreceptor outer segment morphology (MGI Ref ID J:121993)
        • normal organized photoreceptor cell outer segments are not observed at any time
        • composed of membranous whirls arranged in an irregular configuration
        • photoreceptor outer segment degeneration (MGI Ref ID J:26067)
          • largely degenerated
      • decreased retinal photoreceptor cell number (MGI Ref ID J:121993)
        • no photoreceptors were present by 8 months
      • retinal photoreceptor degeneration (MGI Ref ID J:121993)
        • a progressive loss of the photoreceptors
    • retinal outer nuclear layer degeneration (MGI Ref ID J:121993)
      • a progressive loss of outer nuclear layers
  • abnormal retinal pigment epithelium morphology (MGI Ref ID J:121993)
    • granular appearance by 6 weeks
    • focal and diffuse loss of pigment epithelium by 5 months
  • abnormal retinal vasculature (MGI Ref ID J:121993)
    • arteriolar attenuation, venous dilation by 6 weeks
    • severe retinal vessel attenuation and sheathing by 5 months
  • retinal degeneration (MGI Ref ID J:121993)
    • 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
    • only one to two layers of photoreceptor cell nuclei remained at 15-16 postnatal weeks
    • degenerative changes within the inner retina were not observed during first 15 postnatal weeks
    • develop progressive retinal degeneration
  • retinal deposits (MGI Ref ID J:121993)
    • patches of pigment deposits by 5 months
  • hearing/vestibular/ear phenotype
  • abnormal ear morphology (MGI Ref ID J:32415)
    • abnormal bony labyrinth (MGI Ref ID J:26067)
      • 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
    • absent tunnel of Corti (MGI Ref ID J:26067)
    • cochlear hair cell degeneration (MGI Ref ID J:26067)
      • a severely degenerated organ of Corti; no hair cells or supporting cells are identifiable
    • cochlear inner hair cell degeneration (MGI Ref ID J:121993)
      • apparent by 6 postnatal months
    • cochlear outer hair cell degeneration (MGI Ref ID J:26067)
      • only the innermost row of outer hair cells is seen, suggesting a partial loss of outer hair cells
      • 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
    • degeneration of supporting cells (MGI Ref ID J:26067)
      • a severely degenerated organ of Corti; no hair cells or supporting cells are identifiable
      • degeneration of phalangeal and other support cells was also observed
    • organ of Corti degeneration (MGI Ref ID J:26067)
      • a degeneration of organ of Corti in the basal end of the cochlea
      • 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
      • apical half of the cochlea are normal with preservation of hair cells, supporting cells, and afferent dendrites
      • the features of Reissner's membrane, stria vascularis, and the density of nerve fibers within the modiolus are normal
      • Rosenthal's canal, is similar in appearance in all turns
      • neither behavioral nor structural evidence of vestibular abnormalities
  • abnormal hearing physiology (MGI Ref ID J:32415)
    • decreased brainstem auditory evoked potential (MGI Ref ID J:121993)
      • some homozygous mutants showed elevated ABR thresholds to clicks and 32-kHz pips at 3 weeks of age
      • 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
    • impaired hearing (MGI Ref ID J:32415)
      • progressive hearing loss, so that by 5-6 months of age, virtually deaf at 90-100 dB
  • nervous system phenotype
  • abnormal photoreceptor inner segment morphology (MGI Ref ID J:26067)
    • are attenuated
  • abnormal photoreceptor outer segment morphology (MGI Ref ID J:121993)
    • normal organized photoreceptor cell outer segments are not observed at any time
    • composed of membranous whirls arranged in an irregular configuration
    • photoreceptor outer segment degeneration (MGI Ref ID J:26067)
      • largely degenerated
  • cochlear ganglion degeneration (MGI Ref ID J:26067)
    • 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 (MGI Ref ID J:26067)
    • a severely degenerated organ of Corti; no hair cells or supporting cells are identifiable
  • cochlear inner hair cell degeneration (MGI Ref ID J:121993)
    • apparent by 6 postnatal months
  • cochlear outer hair cell degeneration (MGI Ref ID J:26067)
    • only the innermost row of outer hair cells is seen, suggesting a partial loss of outer hair cells
    • 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
  • decreased retinal photoreceptor cell number (MGI Ref ID J:121993)
    • no photoreceptors were present by 8 months
  • retinal photoreceptor degeneration (MGI Ref ID J:121993)
    • a progressive loss of the photoreceptors
  • pigmentation phenotype
  • abnormal retinal pigment epithelium morphology (MGI Ref ID J:121993)
    • granular appearance by 6 weeks
    • focal and diffuse loss of pigment epithelium by 5 months
  • cardiovascular system phenotype
  • abnormal retinal vasculature (MGI Ref ID J:121993)
    • arteriolar attenuation, venous dilation by 6 weeks
    • severe retinal vessel attenuation and sheathing by 5 months

Tubtub/Tubtub

        C57BL/6J-Tubtub
  • growth/size phenotype
  • obese (MGI Ref ID J:13772)
    • increased body weight first becomes obvious at 3-4 months of age in males and 4-6 months in females
  • adipose tissue phenotype
  • increased adipose tissue amount (MGI Ref ID J:13772)
    • the increase in weight is due to excess adipose tissue associated with all fat deposits
  • homeostasis/metabolism phenotype
  • increased circulating insulin level (MGI Ref ID J:13772)
    • plasma immunoreactive insulin is increased to 2 times the normal prior to signs of obesity
    • plasma insulin concentrations increase gradually through out life
    • however, blood sugar levels are normal up to 9 months of age, the oldest mice tested
  • increased glycogen level (MGI Ref ID J:13772)
    • liver glycogen is slightly increased
  • digestive/alimentary phenotype
  • abnormal islet of Langerhans morphology (MGI Ref ID J:13772)
    • islets of Langerhans are moderately enlarged
  • endocrine/exocrine gland phenotype
  • abnormal islet of Langerhans morphology (MGI Ref ID J:13772)
    • islets of Langerhans are moderately enlarged
  • immune system phenotype
  • abnormal Langerhans cell physiology (MGI Ref ID J:13772)
    • islets of Langerhans show indication of hyperactivity in the later stages
  • liver/biliary system phenotype
  • hepatic steatosis (MGI Ref ID J:13772)
    • total liver lipids range from 2-3 times the normal

Gene & Allele Details

Allele Symbol Tubtub
Allele Name tubby
Common Name(s) rd5; tub;
Strain of OriginC57BL/6J
Gene Symbol and Name Tub, tubby candidate gene
Chromosome 7
Gene Common Name(s) rd5; retinal degeneration 5; tubby;
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. [MGI Ref ID J:32415]
 
Allele Symbol Hbbs
Allele Name s
Strain of OriginC57BL/6
Gene Symbol and Name Hbb, hemoglobin beta chain complex
Chromosome 7
Gene Common Name(s) CD113t-C; HBD;

Control Information

  Allele   Control
 Tubtub  Heterozygote from the colony
 
  Considerations for Choosing Controls

Genotyping Protocols

Tubtub

Colony Maintenance

Breeding & HusbandryThis strain was maintained for many years by breeding Hbbp +/Hbbs Tubtub + x Hbbs Tubtub/Hbbs Tubtub or vice versa. Hbb and Tub are approximately 1.5 cM apart on Chromosome 7. Tubby heterozygotes were distinguished from homozygotes by typing for the Hbb allele. This was done by cellulose acetate gel analysis of cystamine treated red blood cell lysates as described by Whitney, 1978. The Hbbs allele yields a single fast migrating band of hemoglobin while the Hbbp allele yields a slow migrating band and a second smaller, trailing band that may actually have cathodal migration on cellulose acetate (but not in starch or acrylamide gels). The mice carrying only the Hbbs allele were presumed homozygous for the Tubtub mutation by linkage; those with both the Hbbs and Hbbp alleles were presumed heterozygous for Tubtub by linkage. In 2004 genotyping of the Tubtub allele by PCR became the standard method for colony maintenance. Recombination can be expected to eventually remove the Hbbp allele from this strain. Heterozygous females are better mothers than homozygous females.

Related Strains

Strains carrying   Hbbs allele
000899   C.B6-Tyr+ Hbbs/J
View Strains carrying   Hbbs     (1 strain)

Strains carrying   Tubtub allele
004176   BKS.B6-Tubtub/Jng
003711   CAST.B6-Tubtub/Jng
View Strains carrying   Tubtub     (2 strains)

View Strains carrying other alleles of Hbb     (10 strains)

Strains carrying other alleles of Tub
003712   B6.CAST-Tub+/J
View Strains carrying other alleles of Tub     (1 strain)

Additional Web Information

JAX® NOTES, Fall 1999; 479. moth1 Gene Protects Tubby Mice From Hearing Loss.

Research Applications

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

Hbbs related

Hematological Research
Hemoglobin Defects

Mouse/Human Gene Homologs
thalassemia, beta

Tubtub related

Diabetes and Obesity Research
Hyperinsulinemia
Obesity With Diabetes (adult onset)
Type 2 Diabetes (NIDDM)

Endocrine Deficiency Research
Adipose Defects
Hypothalamus/Pituitary Defects
Pancreas Defects

Internal/Organ Research
Adipose Defects

Neurobiology Research
Vestibular and Hearing Defects

Sensorineural Research
Retinal Degeneration
Vestibular and Hearing Defects

References

Selected Reference(s)

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

Kleyn PW; Fan W; Kovats SG; Lee JJ; Pulido JC; Wu Y; Berkemeier LR; Misumi DJ; Holmgren L; Charlat O; Woolf EA; Tayber O; Brody T; Shu P; Hawkins F; Kennedy B; Baldini L; Ebeling C; Alperin GD; Deeds J; Lakey ND; Culpepper J; Chen H; Glucksmann-Kuis MA;oore KJ; et al. 1996. Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family. Cell 85(2):281-90. [PubMed: 8612280]  [MGI Ref ID J:32718]

Additional References

Price and Supply Information

Strain Name: B6(Cg)-Tubtub/J
Stock Number: 000562

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Mouse Mutant Resource collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

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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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