Description

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   09-OCT-10 Species laboratory mouse Generation N11+F11 (05-SEP-11) Generation Definitions   Donating Investigator Huda Zoghbi,   Baylor College of Medicine

Description
These mice possess loxP sites on either side of the coding region of the targeted gene. Mice that are homozygous for this floxed allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When crossed with a Cre recombinase-expressing strain, this strain is useful in eliminating tissue-specific expression of the gene. This strain may be useful in further elucidating the role of this gene in cell fate commitment.

Development
A loxP site was inserted 300 bp upstream of the translocation start site, and a second was placed immediately 3' of the coding sequence, followed by an FRT-flanked PGK-neomycin selection cassette. The mutation was introduced to AB2.2 129S7/SvEvBrd-Hprt1⁺-derived embryonic stem (ES) cell line. Mice were crossed with an 129SvEv background hACT-Flpe strain to excise the selection cassette. This strain was backcrossed to C57BL/6 for more than ten generations by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Atoh1

013593	B6.129S-Atoh1tm4.1Hzo/J
013594	B6.129S-Atoh1tm5.1(Cre/PGR)Hzo/J
013595	B6.129S-Atoh1tm6.1Hzo/J
005970	B6.129S7-Atoh1tm2Hzo/J
011104	B6.Cg-Tg(Atoh1-cre)1Bfri/J
007684	STOCK Tg(Atoh1-cre/Esr1*)14Fsh/J

View Strains carrying other alleles of Atoh1     (6 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Atoh1^tm3Hzo/Atoh1^tm3Hzo

        involves: 129S7/SvEvBrd   (conditional)

• nervous system phenotype
• abnormal neuronal precursor proliferation
  • after adenoviral cre infection, proliferation of granule neuron precursors in response to stimulation by sonic hedgehog for 3 days is decreased   (MGI Ref ID J:155047)
• cellular phenotype
• abnormal neuronal precursor proliferation
  • after adenoviral cre infection, proliferation of granule neuron precursors in response to stimulation by sonic hedgehog for 3 days is decreased   (MGI Ref ID J:155047)

View Research Applications

Research Applications

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

Cell Biology Research
Genes Regulating Growth and Proliferation

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Atoh1tm3Hzo
Allele Name		targeted mutation 3, Huda Y Zoghbi
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Atoh1flox; Math1flox;
Mutation Made By		Huda Zoghbi,   Baylor College of Medicine
Strain of Origin		129S7/SvEvBrd-Hprt
ES Cell Line Name		AB2.2
ES Cell Line Strain		129S7/SvEvBrd-Hprt
Gene Symbol and Name		Atoh1, atonal homolog 1 (Drosophila)
Chromosome		6
Gene Common Name(s)		ATH1; HATH1; MATH-1; Math1; RGD1565171; bHLHa14;
Molecular Note		A loxP site was inserted 300 bp upstream of the translation start site and a second loxP site was inserted along with an Frt flanked neo cassette immediately 3' of the coding region. The neo cassette was removed by in vivo Flp-mediated recombination leaving the entire coding region flanked with loxP sites. [MGI Ref ID J:128312]

Genotyping

Genotyping Information

Genotyping Protocols

Atoh1^tm3Hzo, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Shroyer NF; Helmrath MA; Wang VY; Antalffy B; Henning SJ; Zoghbi HY. 2007. Intestine-specific ablation of mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis. Gastroenterology 132(7):2478-88. [PubMed: 17570220]  [MGI Ref ID J:128312]

Additional References

Atoh1^tm3Hzo related

Bjerknes M; Khandanpour C; Moroy T; Fujiyama T; Hoshino M; Klisch TJ; Ding Q; Gan L; Wang J; Martin MG; Cheng H. 2012. Origin of the brush cell lineage in the mouse intestinal epithelium. Dev Biol 362(2):194-218. [PubMed: 22185794]  [MGI Ref ID J:180770]

Bossuyt W; Kazanjian A; De Geest N; Van Kelst S; De Hertogh G; Geboes K; Boivin GP; Luciani J; Fuks F; Chuah M; VandenDriessche T; Marynen P; Cools J; Shroyer NF; Hassan BA. 2009. Atonal homolog 1 is a tumor suppressor gene. PLoS Biol 7(2):e39. [PubMed: 19243219]  [MGI Ref ID J:145954]

Durand A; Donahue B; Peignon G; Letourneur F; Cagnard N; Slomianny C; Perret C; Shroyer NF; Romagnolo B. 2012. Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1). Proc Natl Acad Sci U S A 109(23):8965-70. [PubMed: 22586121]  [MGI Ref ID J:184755]

Flora A; Klisch TJ; Schuster G; Zoghbi HY. 2009. Deletion of Atoh1 disrupts Sonic Hedgehog signaling in the developing cerebellum and prevents medulloblastoma. Science 326(5958):1424-7. [PubMed: 19965762]  [MGI Ref ID J:155047]

Gerbe F; van Es JH; Makrini L; Brulin B; Mellitzer G; Robine S; Romagnolo B; Shroyer NF; Bourgaux JF; Pignodel C; Clevers H; Jay P. 2011. Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium. J Cell Biol 192(5):767-80. [PubMed: 21383077]  [MGI Ref ID J:170320]

Kiesslich R; Goetz M; Angus EM; Hu Q; Guan Y; Potten C; Allen T; Neurath MF; Shroyer NF; Montrose MH; Watson AJ. 2007. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. Gastroenterology 133(6):1769-78. [PubMed: 18054549]  [MGI Ref ID J:135499]

Kim TH; Escudero S; Shivdasani RA. 2012. Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells. Proc Natl Acad Sci U S A 109(10):3932-7. [PubMed: 22355124]  [MGI Ref ID J:182139]

Kim TH; Shivdasani RA. 2011. Genetic Evidence That Intestinal Notch Functions Vary Regionally and Operate through a Common Mechanism of Math1 Repression. J Biol Chem 286(13):11427-33. [PubMed: 21282114]  [MGI Ref ID J:170937]

Klisch TJ; Xi Y; Flora A; Wang L; Li W; Zoghbi HY. 2011. In vivo Atoh1 targetome reveals how a proneural transcription factor regulates cerebellar development. Proc Natl Acad Sci U S A 108(8):3288-93. [PubMed: 21300888]  [MGI Ref ID J:169298]

Li X; Newbern JM; Wu Y; Morgan-Smith M; Zhong J; Charron J; Snider WD. 2012. MEK Is a Key Regulator of Gliogenesis in the Developing Brain. Neuron 75(6):1035-50. [PubMed: 22998872]  [MGI Ref ID J:188328]

Maricich SM; Morrison KM; Mathes EL; Brewer BM. 2012. Rodents rely on Merkel cells for texture discrimination tasks. J Neurosci 32(10):3296-300. [PubMed: 22399751]  [MGI Ref ID J:182735]

Maricich SM; Wellnitz SA; Nelson AM; Lesniak DR; Gerling GJ; Lumpkin EA; Zoghbi HY. 2009. Merkel cells are essential for light-touch responses. Science 324(5934):1580-2. [PubMed: 19541997]  [MGI Ref ID J:149981]

Maricich SM; Xia A; Mathes EL; Wang VY; Oghalai JS; Fritzsch B; Zoghbi HY. 2009. Atoh1-lineal neurons are required for hearing and for the survival of neurons in the spiral ganglion and brainstem accessory auditory nuclei. J Neurosci 29(36):11123-33. [PubMed: 19741118]  [MGI Ref ID J:152678]

McDole JR; Wheeler LW; McDonald KG; Wang B; Konjufca V; Knoop KA; Newberry RD; Miller MJ. 2012. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483(7389):345-9. [PubMed: 22422267]  [MGI Ref ID J:182576]

Morrison KM; Miesegaes GR; Lumpkin EA; Maricich SM. 2009. Mammalian Merkel cells are descended from the epidermal lineage. Dev Biol 336(1):76-83. [PubMed: 19782676]  [MGI Ref ID J:154915]

Noah TK; Kazanjian A; Whitsett J; Shroyer NF. 2010. SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells. Exp Cell Res 316(3):452-65. [PubMed: 19786015]  [MGI Ref ID J:156638]

Pan N; Jahan I; Kersigo J; Kopecky B; Santi P; Johnson S; Schmitz H; Fritzsch B. 2010. Conditional deletion of Atoh1 using Pax2-Cre results in viable mice without differentiated cochlear hair cells that have lost most of the organ of Corti. Hear Res :. [PubMed: 21146598]  [MGI Ref ID J:169044]

Van Keymeulen A; Mascre G; Youseff KK; Harel I; Michaux C; De Geest N; Szpalski C; Achouri Y; Bloch W; Hassan BA; Blanpain C. 2009. Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol 187(1):91-100. [PubMed: 19786578]  [MGI Ref ID J:163216]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL375

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, homozygotes may be bred.
Mating System	Homozygote x Homozygote         (Female x Male)   09-OCT-10
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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'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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