JAX Mouse Strain Datasheet - 005699

STOCK Tg(tetO-Ipf1,EGFP)956.6Macd/J

Stock No:: 005699 |; Tg^Pdx1

Transgenic

Cryo Recovery

Overview

Also Known As: Tg^Pdx1

These Tg^Pdx1 mice express a transgene containing EGFP and Ipf1 after crossing with a strain expressing tetracycline-transactivator (tTA) under the control of a tissue-specific promoter. Such double mutant mice may be useful in studies of pancreatic endocrine/exocrine function and diabetes.

Donating Investigator

Raymond MacDonald, UTSW Medical Center

Genetic overview

Genetic Background	Generation

Gnat2^cpfl3

Allele Type	Gene Symbol	Gene Name
Spontaneous	Gnat2	guanine nucleotide binding protein, alpha transducing 2

Tg(tetO-Ipf1,EGFP)956.6Macd

Allele Type
Transgenic (Inducible, Inserted expressed sequence, Reporter)

View Genetics

Research Applications

Endocrine Deficiency Research
Metabolism Research
Research Tools
Sensorineural Research

View All Research Applications

Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Important Note

This strain may be homozygous for Gnat2^cpfl3, cone photoreceptor function loss 3, which affects bright light (photopic) vision.

Detailed Description

Mice hemizygous for the transgene are viable, fertile, normal in size, and do not display any behavioral abnormalities. At the Jackson Laboratory, no homozygous mice were produced from mating hemizygotes together, suggesting that homozygous transgenic animals die in utero. Expression of the bicistronic transgene is under the regulation of a tetracycline promoter element (TRE; tetO). By themselves, these transgenic mice do not express EGFP, but when these mice are mated with a second transgenic strain expressing tetracycline-transactivator (tTA) protein under the control of a tissue-specific promoter, Ipf1 and EGFP are highly expressed in the appropriate tissue of bitransgenic offspring.

This mouse was originally designed to be mated to an apancreatic targeted mutant with tTA_off in place of the endogenous Ipf1 gene (see Stock No. 005701). The combined mutations allow normal pancreatic development and function until doxycycline treatment renders the double mutant mouse conditionally null for Ipf1 expression. Using these double transgenic mice, pancreatic developmental can be arrested at any stage during embryonic development or in adult mice. Such double mutant mice may be useful in studies of pancreatic endocrine/exocrine function and diabetes. Tg(tetO-Ipf1,EGFP)956.6Macd transgenic mice also may be bred with other tTA transgenic strains for conditional mutation analysis.

Development

A bicistronic transgenic vector was generated containing an Ipf1 minigene (both exons linked with a shortened intron and preceded by a truncated 5' untranslated region) and an internal ribosome entry site-linked enhanced green fluorescent protein (EGFP) all under transcriptional control of a tetracycline-responsive regulatory element (TRE). Transgenic mice were generated by pronuclear injection of the construct into fertilized [C57BL/6 x SJL] F2 hybrid embryos. Two-cell stage eggs were implanted into pseudopregnant foster mothers. Founder line 956.6 was obtained and was maintained by transgenic positive sibling intercross. At some point, transgenic mice were bred to B6;129 mice with a targeted mutation. The targeted mutation was selected against in subsequent breedings, and the transgenic line was again maintained by hemizygous intercrosses prior to cryopreservation.

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Transgenic mice do not express EGFP until a tetracycline-transactivator (tTA) protein is introduced; after which point Ipf1 and EGFP from the transgene are highly expressed. Transgenic mice have low level transgene expression (mRNA) in liver, kidney, spleen, and salivary gland.

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Holland AM; Hale MA; Kagami H; Hammer RE; MacDonald RJ. 2002. Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci U S A 99(19):12236-41. PubMed: 12221286 MGI: J:79206

View All References

Genetics

Gnat2^cpfl3

Allele Symbol: Gnat2^cpfl3

Allele Name	cone photoreceptor function loss 3
Allele Type	Spontaneous
Allele Synonym(s)	no cones
Gene Symbol and Name	Gnat2, guanine nucleotide binding protein, alpha transducing 2
Gene Synonym(s)	ACHM4; AW490837; GNATC; Gnat-2; Gnat-2; Gt-2; Tcalpha; expressed sequence AW490837
Strain of Origin	various
Chromosome	3
General Note	This allele has been detected in the following strains either by genotyping or complementation testing: ALS/LtJ, SENCARA/PtJ, SENCARB/PtJ, SENCARC/PtJ, PN/nBSwUmabJ. (J:122428) The allele has also been reported in NMRI and CD1 (Lluis Montoliu, J:212307)
Molecular Note	A single nucleotide substitution of G to A at position 598 in exon 6. This mutation converts codon 200 from aspartic acid to asparagine.

Tg(tetO-Ipf1,EGFP)956.6Macd

Allele Symbol: Tg(tetO-Ipf1,EGFP)956.6Macd

Allele Name	transgene insertion 956-6, Raymond J MacDonald
Allele Type	Transgenic (Inducible, Inserted expressed sequence, Reporter)
Allele Synonym(s)	Pdx1-EGFP; Pdx1-GFP; Pdx1^Tg; Tg^Pdx1; tTA-responsive Pdx1-EGFP; tetO-Pdx1; tetO-Pdx1-EGFP; tetO-Pdx1/EGFP; tetO/Pdx1/EGFP
Gene Symbol and Name	Tg(tetO-Ipf1,EGFP)956.6Macd, transgene insertion 956-6, Raymond J MacDonald
Gene Synonym(s)	Pdx1-EGFP; Pdx1-GFP; Pdx1^Tg; Tg^Pdx1; tTA-responsive Pdx1-EGFP; tetO-Pdx1; tetO-Pdx1-EGFP; tetO-Pdx1/EGFP; tetO/Pdx1/EGFP
Promoter	tetO, tet operator,
Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Transgenic mice do not express EGFP until a tetracycline-transactivator (tTA) protein is introduced; after which point Ipf1 and EGFP from the transgene are highly expressed. Transgenic mice have low level transgene expression (mRNA) in liver, kidney, spleen, and salivary gland.
Strain of Origin	(C57BL/6 x SJL)F2
Chromosome	UN
Molecular Note	A transgenic vector containing an Ipf1 minigene (both exons of Ipf1 linked by a shortened exon and preceded by a truncated 5' UTR and an IRES-linked EGFP reporter) under control of seven direct repeats of the tetracycline operator (tetO) fused to the human cytomegalovirus (hCMV) immediate early promoter. High expression of Ipf1 and EGFP is induced by introduction of the tetracycline-transactivator protein by breeding with an appropriate mouse line.
Mutations Made By	Raymond MacDonald, UTSW Medical Center

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Endocrine Deficiency Research
- Pancreas Defects
Metabolism Research
- Enzyme Deficiency
  - exocrine pancreatic insufficiency
Research Tools
- Endocrine Deficiency Research
- Fluorescent Proteins
- Genetics Research
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: Tetop Tet System
  - Tissue/Cell Markers
  - Tissue/Cell Markers: multiple
  - Tissue/Cell Markers: pancreatic beta cells
- Tet Expression Systems
  - tTA/rtTA Responsive Strains

Genotype: GFP related

Research Tools
- Fluorescent Proteins

Genotype: Gnat2^cpfl3 related

Sensorineural Research
- Eye Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Pdx1^tm1Macd/Pdx1^tm1Macd Tg(tetO-Ipf1,EGFP)956.6Macd/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

homeostasis/metabolism phenotype

decreased circulating glucose level
- 14 days after doxycycline withdrawal after 14 days of treatment resulted in a significant decrease in blood glucose levels with 4/5 mice becoming normoglycemic by 28 days

decreased insulin secretion
- there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters

impaired glucose tolerance
- adult transgenic rescue animals treated with doxycycline for 14 days exhibit a defective response to glucose challenge compared to wild-type, non mutant transgenic, or untreated rescue mice
- when adult mice are treated with doxycycline for 0, 7, 14, or 21 days, mice show an increased early glucose response within 7 days of start of treatment and ability to recover from glucose challenge is impaired compared to untreated transgenics where glucose levels recover to basal levels within 3 hours; by 14 days of doxycycline treatment, mice have diabetescose levels recover to basal levels within 3 hours; by 14 days of doxycycline treatment, mice have diabetes

increased circulating glucose level
- with doxycycline treatment for 21 day, adult rescue mice show a 4-fold increase in fasting blood glucose to diabetic levels

increased glucagon secretion
- in doxycycline-treated mice there is an increase in glucagons-positive cells

endocrine/exocrine gland phenotype

abnormal pancreas development
- pancreas of transgenic rescue newborn mice is 50% the size of a normal wild-type neonatal pancreas
- treatment of pregnant mice with doxycycline from the first day of pregnancy through parturition prevents formation of the pancreas in mice with the transgenic rescue genotype
- treatment on E11.5 arrests pancreatic development ~36 hours later; at birth the underdeveloped remnant consisted of a large and extended duct with several terminal, aborted, ductal buds with ducts lined with a single layer of primitive epithelial cells and with no acinar or islet tissued with no acinar or islet tissue

abnormal pancreatic beta cell morphology
- after 14 or 28 days of dox treatment there are, still present, beta cells which lack insulin

decreased insulin secretion
- there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters

increased glucagon secretion
- in doxycycline-treated mice there is an increase in glucagons-positive cells

small pancreatic islets
- after dox treatment for 14 days, there is a significant decrease in islet area compared to wild-type

cellular phenotype

increased cell proliferation
- foci of duct proliferation are present in mice after 14 days of doxycycline treatment and become more prominent with continued treatment

References

Holland AM; Hale MA; Kagami H; Hammer RE; MacDonald RJ. 2002. Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci U S A 99(19):12236-41. PubMed: 12221286 MGI: J:79206

Additional References

Chang B; Dacey MS; Hawes NL; Hitchcock PF; Milam AH; Atmaca-Sonmez P; Nusinowitz S; Heckenlively JR. 2006. Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2. Invest Ophthalmol Vis Sci 47(11):5017-21. PubMed: 17065522 MGI: J:122428

Additional - Gnat2^cpfl3 related

Alexander JJ; Umino Y; Everhart D; Chang B; Min SH; Li Q; Timmers AM; Hawes NL; Pang JJ; Barlow RB; Hauswirth WW. 2007. Restoration of cone vision in a mouse model of achromatopsia. Nat Med 13(6):685-7. PubMed: 17515894 MGI: J:121897
Allen AE; Cameron MA; Brown TM; Vugler AA; Lucas RJ. 2010. Visual responses in mice lacking critical components of all known retinal phototransduction cascades. PLoS One 5(11):e15063. PubMed: 21124780 MGI: J:167121
Altimus CM; Guler AD; Alam NM; Arman AC; Prusky GT; Sampath AP; Hattar S. 2010. Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities. Nat Neurosci 13(9):1107-12. PubMed: 20711184 MGI: J:165280
Chang B; Dacey MS; Hawes NL; Hitchcock PF; Milam AH; Atmaca-Sonmez P; Nusinowitz S; Heckenlively JR. 2006. Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2. Invest Ophthalmol Vis Sci 47(11):5017-21. PubMed: 17065522 MGI: J:122428
Chang B; Hawes NL; Hurd RE; Wang J; Howell D; Davisson MT; Roderick TH; Nusinowitz S; Heckenlively JR. 2005. Mouse models of ocular diseases. Vis Neurosci 22(5):587-93. PubMed: 16332269 MGI: J:156373
Chang B; Hurd R; Wang J; Nishina P. 2013. Survey of common eye diseases in laboratory mouse strains. Invest Ophthalmol Vis Sci 54(7):4974-81. PubMed: 23800770 MGI: J:198916
Deng WT; Sakurai K; Liu J; Dinculescu A; Li J; Pang J; Min SH; Chiodo VA; Boye SL; Chang B; Kefalov VJ; Hauswirth WW. 2009. Functional interchangeability of rod and cone transducin alpha-subunits. Proc Natl Acad Sci U S A 106(42):17681-6. PubMed: 19815523 MGI: J:153749
IMGC. 2014. Abstracts for the IMGC2014 meeting (October, 2014) :. MGI: J:212307
Jones RS; Pedisich M; Carroll RC; Nawy S. 2014. Spatial organization of AMPAR subtypes in ON RGCs. J Neurosci 34(2):656-61. PubMed: 24403163 MGI: J:205576
Ke JB; Wang YV; Borghuis BG; Cembrowski MS; Riecke H; Kath WL; Demb JB; Singer JH. 2014. Adaptation to background light enables contrast coding at rod bipolar cell synapses. Neuron 81(2):388-401. PubMed: 24373883 MGI: J:250020
Keenan WT; Rupp AC; Ross RA; Somasundaram P; Hiriyanna S; Wu Z; Badea TC; Robinson PR; Lowell BB; Hattar SS. 2016. A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction. Elife 5:. PubMed: 27669145 MGI: J:238084
Laprell L; Tochitsky I; Kaur K; Manookin MB; Stein M; Barber DM; Schon C; Michalakis S; Biel M; Kramer RH; Sumser MP; Trauner D; Van Gelder RN. 2017. Photopharmacological control of bipolar cells restores visual function in blind mice. J Clin Invest 127(7):2598-2611. PubMed: 28581442 MGI: J:244965
Naarendorp F; Esdaille TM; Banden SM; Andrews-Labenski J; Gross OP; Pugh EN Jr. 2010. Dark light, rod saturation, and the absolute and incremental sensitivity of mouse cone vision. J Neurosci 30(37):12495-507. PubMed: 20844144 MGI: J:164666
Nathan J; Reh R; Ankoudinova I; Ankoudinova G; Chang B; Heckenlively J; Hurley JB. 2006. Scotopic and photopic visual thresholds and spatial and temporal discrimination evaluated by behavior of mice in a water maze. Photochem Photobiol 82(6):1489-94. PubMed: 16683905 MGI: J:238265
Nusinowitz S; Ridder WH 3rd; Ramirez J. 2007. Temporal response properties of the primary and secondary rod-signaling pathways in normal and Gnat2 mutant mice. Exp Eye Res 84(6):1104-14. PubMed: 17408617 MGI: J:126462
Prigge CL; Yeh PT; Liou NF; Lee CC; You SF; Liu LL; McNeill DS; Chew KS; Hattar S; Chen SK; Zhang DQ. 2016. M1 ipRGCs Influence Visual Function through Retrograde Signaling in the Retina. J Neurosci 36(27):7184-97. PubMed: 27383593 MGI: J:234637
Sakami S; Kolesnikov AV; Kefalov VJ; Palczewski K. 2014. P23H opsin knock-in mice reveal a novel step in retinal rod disc morphogenesis. Hum Mol Genet 23(7):1723-41. PubMed: 24214395 MGI: J:207143
Szikra T; Trenholm S; Drinnenberg A; Juttner J; Raics Z; Farrow K; Biel M; Awatramani G; Clark DA; Sahel JA; da Silveira RA; Roska B. 2014. Rods in daylight act as relay cells for cone-driven horizontal cell-mediated surround inhibition. Nat Neurosci 17(12):1728-35. PubMed: 25344628 MGI: J:219420
Tikidji-Hamburyan A; Reinhard K; Seitter H; Hovhannisyan A; Procyk CA; Allen AE; Schenk M; Lucas RJ; Munch TA. 2015. Retinal output changes qualitatively with every change in ambient illuminance. Nat Neurosci 18(1):66-74. PubMed: 25485757 MGI: J:219606
Tikidji-Hamburyan A; Reinhard K; Storchi R; Dietter J; Seitter H; Davis KE; Idrees S; Mutter M; Walmsley L; Bedford RA; Ueffing M; Ala-Laurila P; Brown TM; Lucas RJ; Munch TA. 2017. Rods progressively escape saturation to drive visual responses in daylight conditions. Nat Commun 8(1):1813. PubMed: 29180667 MGI: J:256237
Umino Y; Solessio E; Barlow RB. 2008. Speed, spatial, and temporal tuning of rod and cone vision in mouse. J Neurosci 28(1):189-98. PubMed: 18171936 MGI: J:131050
Wang YV; Weick M; Demb JB. 2011. Spectral and temporal sensitivity of cone-mediated responses in mouse retinal ganglion cells. J Neurosci 31(21):7670-81. PubMed: 21613480 MGI: J:191557
Won J; Shi LY; Hicks W; Wang J; Hurd R; Naggert JK; Chang B; Nishina PM. 2011. Mouse model resources for vision research. J Ophthalmol 2011:391384. PubMed: 21052544 MGI: J:166679
Zhao X; Stafford BK; Godin AL; King WM; Wong KY. 2014. Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells. J Physiol 592(Pt 7):1619-36. PubMed: 24396062 MGI: J:219912

Additional - Tg(tetO-Ipf1,EGFP)956.6Macd related

Gauthier BR; Wiederkehr A; Baquie M; Dai C; Powers AC; Kerr-Conte J; Pattou F; MacDonald RJ; Ferrer J; Wollheim CB. 2009. PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. Cell Metab 10(2):110-8. PubMed: 19656489 MGI: J:151308
Hale MA; Kagami H; Shi L; Holland AM; Elsasser HP; Hammer RE; MacDonald RJ. 2005. The homeodomain protein PDX1 is required at mid-pancreatic development for the formation of the exocrine pancreas. Dev Biol 286(1):225-37. PubMed: 16126192 MGI: J:103522
Holland AM; Gonez LJ; Naselli G; Macdonald RJ; Harrison LC. 2005. Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of beta-cells in the adult pancreas. Diabetes 54(9):2586-95. PubMed: 16123346 MGI: J:101742

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(tetO-Ipf1,EGFP)956.6Macd

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Also Known As: TgPdx1

Donating Investigator

Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Gnat2cpfl3

Allele Symbol: Gnat2cpfl3

Tg(tetO-Ipf1,EGFP)956.6Macd

Allele Symbol: Tg(tetO-Ipf1,EGFP)956.6Macd

Disease Terms

Research Areas By Genotype

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

Genotype: GFP related

Genotype: Gnat2cpfl3 related

Mammalian Phenotype Terms by Genotype

Genotype: Pdx1tm1Macd/Pdx1tm1Macd Tg(tetO-Ipf1,EGFP)956.6Macd/0involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

homeostasis/metabolism phenotype

endocrine/exocrine gland phenotype

cellular phenotype

References

Additional References

Additional - Gnat2cpfl3 related

Additional - Tg(tetO-Ipf1,EGFP)956.6Macd related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: Tg^Pdx1

Gnat2^cpfl3

Allele Symbol: Gnat2^cpfl3

Genotype: Gnat2^cpfl3 related

Genotype: Pdx1^tm1Macd/Pdx1^tm1Macd Tg(tetO-Ipf1,EGFP)956.6Macd/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Additional - Gnat2^cpfl3 related