Strain Name:

B6.FVB-Tg(GNAT2-Dta)98Wwk/J

Stock Number:

006576

Availability:

Repository- Live

Use Restrictions Apply, see Purchasing Information

Description

Strain Information

Former Names B6.FVB-Tg(GNAT2-DTA)98Wwk/J    (Changed: 07-FEB-07 )
Type Congenic; Mutant Strain; Transgenic;
Mating System+/+ sibling x Hemizygote         (Female x Male)
Specieslaboratory mouse
GenerationN10+N1+F1 (28-DEC-07)
 
Donating Investigator Shao-Ling Fong,   Indiana University

Description
Mice hemizygous for this "Trc-Tox176" transgene (also called "h-GNAT2pro-DTA") are viable and fertile. Expression of diphtheria toxin (DTA) from the transgene is similar to that of endogenous GNAT2, leading to ablation of both rod and cone photoreceptor development in the ventral retina (the abnormality is a result of abnormal cellular development rather than a consequence of retinal degeneration). The dorsal retina has nearly normal development of rods, but the development of cones is limited to about 10%. These transgenic mice exhibit an absence of cone photoreceptors in the retina, as well as the concomitant absence of rod photoreceptors in the ventral retina. The mice may be useful in studies of photoreceptor development, photoreceptor-related retinal diseases, and to profile photoreceptor genes in adult and in developmental stages.

Development
A 2.4 kb transgenic construct was designed placing a 277 bp cone photoreceptor cell-specific promoter of human cone transducin alpha-subunit (GNAT2) upstream of a 680 bp attenuated diphtheria toxin A-chain gene (Tox176), and a 214 bp enhancer element from human interphotoreceptor retinoid-binding protein (IRBP) downstream of an SV40 intron and poly A site. This transgene was microinjected into single-cell stage FVB/N embryos. Since FVB/N mice have a recessive mutation at the rd (or Pde6brd1) locus, founder line Tg98 mice were bred with C57BL/6J mice to establish stable "Trc-Tox176" transgenic mouse lines. Male transgenic mice were mated with C57BL/6J females for approximately 10 generations prior to arrival at The Jackson Laboratory.

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Dta
002384   FVB/N-Tg(UcpDta)1Kz/J
008168   STOCK Tg(tetO-DTA)1Gfi/J
View Strains carrying other alleles of Dta     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tg(GNAT2-Dta)98Wwk/0

        involves: C57BL/6J * FVB/N
  • nervous system phenotype
  • abnormal retinal photoreceptor morphology (MGI Ref ID J:102232)
    • photoreceptors are noticeably absent in ventral portion of retina
    • photoreceptor shape becomes more distorted in ventral region of transitional zone
    • partial and malformed cells are still present in transitional zone when normal retinal cells reach maturity (P12-P23), and persist in older animals
    • abnormal photoreceptor inner segment morphology (MGI Ref ID J:102232)
      • thinning of inner segment layer (ISL) accompanies reduction in photoreceptors
      • in photoreceptors in ventral region of transitional zone, length of inner segment becomes steadily attenuated, such that remaining cells have truncated and thickened inner segment with distorted shapes
    • abnormal photoreceptor outer segment morphology (MGI Ref ID J:116305)
      • thinner than in wild-type
      • thinning of outer segment layer (OSL) accompanies reduction in photoreceptors at P23
      • in photoreceptors in ventral region of transitional zone, length of inner segment becomes steadily attenuated
    • absent retinal cone cells (MGI Ref ID J:102232)
      • at P23 and P60, cone photoreceptors are not distinguishable in rod population
    • decreased retinal rod cell number (MGI Ref ID J:102232)
      • at P23, rods are found only in dorsal half of mutant retina
      • absent retinal rod cells (MGI Ref ID J:102232)
        • rods are typically absent in most of ventral retina at P60
    • retinal photoreceptor degeneration (MGI Ref ID J:116305)
      • number of photoreceptors decreases with age
      • retinal cone cell degeneration (MGI Ref ID J:116305)
        • retina begins to lose cone cells at P8, and at P21, cone cells are absent among remaining photoreceptor cells
      • retinal rod cell degeneration (MGI Ref ID J:116305)
        • age-related rod degeneration begins at P9, and proceeds from central retina to peripheral retina
  • gliosis (MGI Ref ID J:102232)
    • a gliosis marker is detected in ventral portion spanning the retina
  • vision/eye phenotype
  • abnormal retina morphology (MGI Ref ID J:102232)
    • middle portion of transgenic retinal contains transitional zone extending dorsally and ventrally from the optic disk; in outer nuclear layer (ONL) of this zone, photoreceptor nuclei decrease
    • retinal becomes thinner in more ventral regions at P23, containing fewer cellular and synaptic layers
    • at P8, immature photorecptor cells with partially formed inner segments are segregated from neurons in a newly-formed inner nuclear layer (INL); a synaptic outer plexiform layer is found between these layers; in ventral retina, such differentiation has not occurred
    • cells with small rounded somas and lacking segmentation line distal inner nuclear layer/RPE junction
    • by P30-68, radial thickness of dorsal retina decreases to ~80-100 um, while ventral region is dramatically thinner (~45-55 um) compared to wild-type retina radial thickness of 110-130 um
    • by P360, dorsal retina is 70-100 um thick, while ventral region remains 45-55 um
    • abnormal retinal photoreceptor morphology (MGI Ref ID J:102232)
      • photoreceptors are noticeably absent in ventral portion of retina
      • photoreceptor shape becomes more distorted in ventral region of transitional zone
      • partial and malformed cells are still present in transitional zone when normal retinal cells reach maturity (P12-P23), and persist in older animals
      • abnormal photoreceptor inner segment morphology (MGI Ref ID J:102232)
        • thinning of inner segment layer (ISL) accompanies reduction in photoreceptors
        • in photoreceptors in ventral region of transitional zone, length of inner segment becomes steadily attenuated, such that remaining cells have truncated and thickened inner segment with distorted shapes
      • abnormal photoreceptor outer segment morphology (MGI Ref ID J:116305)
        • thinner than in wild-type
        • thinning of outer segment layer (OSL) accompanies reduction in photoreceptors at P23
        • in photoreceptors in ventral region of transitional zone, length of inner segment becomes steadily attenuated
      • absent retinal cone cells (MGI Ref ID J:102232)
        • at P23 and P60, cone photoreceptors are not distinguishable in rod population
      • decreased retinal rod cell number (MGI Ref ID J:102232)
        • at P23, rods are found only in dorsal half of mutant retina
        • absent retinal rod cells (MGI Ref ID J:102232)
          • rods are typically absent in most of ventral retina at P60
      • retinal photoreceptor degeneration (MGI Ref ID J:116305)
        • number of photoreceptors decreases with age
        • retinal cone cell degeneration (MGI Ref ID J:116305)
          • retina begins to lose cone cells at P8, and at P21, cone cells are absent among remaining photoreceptor cells
        • retinal rod cell degeneration (MGI Ref ID J:116305)
          • age-related rod degeneration begins at P9, and proceeds from central retina to peripheral retina
    • thin retinal outer nuclear layer (MGI Ref ID J:116305)
      • at P9, outer nuclear layer (ONL) of central retina is thinner than in wild-type; ONL is 3-4 layer thick compared to 9-10 in wild-type
      • at P30, ONL of central retina consists of only one layer of photoreceptor cell bodies; in peripheral retina, ONL contains 2-3 layers of cell bodies
      • at P60, entire ONL at very center of retina has disappeared; in peripheral retina, only one cell layer remains
      • at P180, in central and peripheral regions in ventral portion of retina, ONL is absent
      • at P30-68, 8-10 rows of nuclei are present in dorsal ONL, compared to 10-12 in dorsal and ventral wild-type retina
      • by P360, there are 7-8 rows of nuclei in ONL
      • in transitional zone, photoreceptor nuclei in ONL decreases from 8-9 rows dorsally to 0 ventrally
    • thin retinal outer plexiform layer (MGI Ref ID J:102232)
      • outer plexiform layer (OPL) is thinner

Research Applications

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

Developmental Biology Research
Eye Defects

Research Tools
Sensorineural Research (retinal degeneration)

Sensorineural Research
Eye Defects
Retinal Degeneration

Genes & Alleles

Gene & Allele Information

Allele Symbol Tg(GNAT2-Dta)98Wwk
Allele Name transgene insertion 98, Winston W-Y Kao
Common Name(s) Tg98; Trc-Tox176; h-GNAT2pro-DTA;
Mutation Made By Winston W.Y. Kao,   University of Cincinnati
Strain of OriginFVB/N
Expressed Gene Dta, Diphtheria toxin A chain,
Brown fat specific expression of the A-chain of diptheria toxin (DTA) resulting in ablation of brown fat.
Promoter GNAT2, guanine nucleotide binding protein (G protein), alpha transducing activity polypeptide 2, human
General Note Of four transgenic lines derived from independent germline-transmitting transgenic founder mice, only the line descended from male founder C98, estimated by Southern blot analysis to carry approximately 10 tandemly-arrayed copies of the transgene, exhibited a retinal phenotype. Lines derived from female founders C8, C12 and C13, each estimated to carry two tandemly integrated copies of the transgene, exhibited no retinal phenotype even at 180 days of age and so were not characterized further.
Molecular Note The 2.4-kb transgenic construct comprises a 277-base pair (-bp) DNA fragment containing the cone photoreceptor cell-specific promoter from the human GNAT2 gene upstream of a 680-bp cDNA encoding an attenuated diphtheria toxin A-chain followed by an SV40 intron and polyadenylation signal and a 214-bp enhancer element from the human RBP3 gene. While RT-PCR detects transcripts from the endogenous Gnat1 and Gnat2 genes, (encoding the rod and cone transducin alpha subunits, respectively) in wild-type retinas from postnatal day 8 (P8) onward, neither endogenous Gnat2 transcripts nor transgene-derived mRNA are detected in retinas from mice of transgenic line 98 at P8 or later. [MGI Ref ID J:116305]

Genotyping

Genotyping Information

Genotyping Protocols

Generic RD, STD PCR, vers. 1
Generic RD, STD PCR, vers. 1
Tg(GNAT2-Dta)98Wwk, , vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Fong SL; Criswell MH; Belecky-Adams T; Fong WB; McClintick JN; Kao WW; Edenberg HJ. 2005. Characterization of a transgenic mouse line lacking photoreceptor development within the ventral retina. Exp Eye Res 81(4):376-88. [PubMed: 16054133]  [MGI Ref ID J:102232]

Ying S; Jansen HT; Lehman MN; Fong SL; Kao WW. 2000. Retinal degeneration in cone photoreceptor cell-ablated transgenic mice. Mol Vis 6:101-8. [PubMed: 10869099]  [MGI Ref ID J:116305]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygous mice are bred with wildtype siblings or C57BL/6J inbred mice.
Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations             View   International   Pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $236.40Female or MaleHemizygous for Tg(GNAT2-Dta)98Wwk
Pairs /Price*Pair Genotype
$288.65Hemizygous for Tg(GNAT2-Dta)98Wwk x Noncarrier
$288.65Noncarrier x Hemizygous for Tg(GNAT2-Dta)98Wwk
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes

Pricing for International shipping destinations             View   USA, Canada and Mexico   Pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $307.40Female or MaleHemizygous for Tg(GNAT2-Dta)98Wwk
Pairs /Price*Pair Genotype
$375.30Hemizygous for Tg(GNAT2-Dta)98Wwk x Noncarrier
$375.30Noncarrier x Hemizygous for Tg(GNAT2-Dta)98Wwk
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.
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