Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation ?pN1 Generation Definitions   Donating Investigator Kevin Campbell,   University of Iowa

Description
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 bred to mice with a Cre recombinase gene under the control of a promoter of interest, exon 2 of the targeted gene and a neomycin cassette are deleted in the tissue of interest. These mutant mice may be useful in studying muscle disease and regeneration.

When bred to a strain expressing Cre recombinase under the control of the human glial fibrillary acidic protein promoter (GFAP) (see Stock No. 004600 for example), this mutant mouse strain may be useful in studies of brain abnormalities observed in congenital muscular dystrophies.

When bred to a strain expressing Cre recombinase in the nervous system (see Stock No. 003771 for example), this mutant mouse strain may be useful in studies of retinal physiology.

When bred to mice carrying Tg(Mpz-cre)26Mes (see Stock No. 017927 for example) Cre recombinase expression in Schwann cells results in abnormal folding or the myelin sheath and demyelination.

Development
A targeting vector was used to introduce a loxP site downstream of exon 2 and insert a floxed neo cassette in the upstream intron. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. ES cells were injected into blastocysts. Chimeric animals were backcrossed to C57BL/6 for six generations by the donating laboratory

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Dag1^tm2Kcam allele

006835

129-Dag1tm2Kcam/J

View Strains carrying   Dag1^tm2Kcam     (1 strain)

Strains carrying other alleles of Dag1

009652	B6.129(Cg)-Dag1tm2.1Kcam/J
006836	B6.129-Dag1tm1Kcam/J

View Strains carrying other alleles of Dag1     (2 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Muscular Dystrophy-Dystroglycanopathy (limb-Girdle), Type C, 9; MDDGC9   (DAG1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Dag1^tm2Kcam/Dag1^tm2Kcam Tg(GFAP-cre)25Mes/0

        involves: 129S1/Sv * 129X1/SvJ * FVB/N   (conditional)

• craniofacial phenotype
• megacephaly   (MGI Ref ID J:86901)
• nervous system phenotype
• abnormal brain morphology
  • fusion of the cerebral interhemispheric fissure and adjacent cerebellar folia   (MGI Ref ID J:86901)
  • malformations resembling polymicrogyria   (MGI Ref ID J:86901)
• • abnormal cerebellar cortex morphology
    • cerebellar cortical surfaces show widespread discontinuities of the glia limitans (pial surface basal lamina) accompanied by glial neuronal heterotopia within the leptomeninges   (MGI Ref ID J:86901)
  • abnormal cerebellum development
    • granule cells are observed in the subrarachnoid space during postnatal cerebellar development indicating aberrant migration of granule cells   (MGI Ref ID J:86901)
  • abnormal cerebral cortex morphology
    • cerebral cortical surfaces show widespread discontinuities of the glia limitans (pial surface basal lamina) accompanied by glial neuronal heterotopia within the leptomeninges   (MGI Ref ID J:86901)
  • • abnormal stratification in cerebral cortex
      • multifocal disarray of neuronal layering in the cerebral cortex   (MGI Ref ID J:86901)
  • abnormal hippocampus CA1 region morphology
    • some mutants show minor dispersion of neuronal cell bodies in the CA1 region   (MGI Ref ID J:86901)
  • abnormal hippocampus granule cell layer
    • some mutants show focal irregularities of the dentate granule cell layer in the hippocampus   (MGI Ref ID J:86901)
  • increased brain size
    • about 20% increase in brain size   (MGI Ref ID J:86901)
• abnormal neuronal migration
  • cerebral, cerebellar and brain stem neuronal migration abnormalities   (MGI Ref ID J:86901)
• abnormal subarachnoid space morphology
  • the normally open subarachnoid space is filled with heterotopic astrocytic and neuronal processes   (MGI Ref ID J:86901)
• astrocytosis
  • GFAP-immunoreactive astrocytes are prominent in the cerebral cortex, indicating gliosis   (MGI Ref ID J:86901)
• reduced long term potentiation
  • induction of long-term potentiation (LTP) by high-frequency stimulation is blunted in hippocampal slices, however baseline neurotransmission is unaffected and presynaptic neurotransmitter release is not affected   (MGI Ref ID J:86901)
• vision/eye phenotype
• abnormal rod electrophysiology
  • significantly reduced positive scotopic threshold response   (MGI Ref ID J:158199)
  • significantly increased negative scotopic threshold response   (MGI Ref ID J:158199)
  • the b-wave responses are severely attenuated   (MGI Ref ID J:158199)
• cellular phenotype
• abnormal neuronal migration
  • cerebral, cerebellar and brain stem neuronal migration abnormalities   (MGI Ref ID J:86901)

Dag1^tm2Kcam/Dag1^tm2Kcam Tg(Mpz-cre)26Mes/0

        involves: 129 * C57BL/6 * FVB/N   (conditional)

• nervous system phenotype
• abnormal action potential
  • reduced motor action potential amplitude   (MGI Ref ID J:137852)
• abnormal myelin sheath morphology
  • abnormally folded myelin with loops, infolding and outfolding is seen in sciatic nerves   (MGI Ref ID J:137852)
• abnormal nerve conduction   (MGI Ref ID J:137852)
• • decreased nerve conduction velocity   (MGI Ref ID J:137852)
• demyelination
  • hypomyelination of the ventral roots   (MGI Ref ID J:137852)
  • decrease in myelination becomes evident with age and at 12 months of age includes signs of acute demyelination, myelin degeneration, macrophage infiltration, and remyelination   (MGI Ref ID J:137852)

Dag1^tm2Kcam/Dag1^tm2Kcam Tg(Nes-cre)1Kln/0

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL   (conditional)

• vision/eye phenotype
• abnormal rod electrophysiology
  • the positive scotopic threshold response is significantly reduced   (MGI Ref ID J:158199)
  • the b-wave responses are severely attenuated   (MGI Ref ID J:158199)
• blindness
  • in the Morris water maze and visual cliff test   (MGI Ref ID J:158199)
• buphthalmos   (MGI Ref ID J:158199)
• corneal opacity
  • corneal opacities   (MGI Ref ID J:158199)
• iris synechia
  • synechia of the iris and cornea   (MGI Ref ID J:158199)
• microphthalmia   (MGI Ref ID J:158199)
• mydriasis
  • pupils are dilated but responsive to light   (MGI Ref ID J:158199)

View Research Applications

Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dag1tm2Kcam
Allele Name		targeted mutation 2, Kevin P Campbell
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		DG (lox); DG-flox; DGlox; Dag1L; Dag1flox; Dag1lox;
Mutation Made By		Kevin Campbell,   University of Iowa
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Dag1, dystroglycan 1
Chromosome		9
Gene Common Name(s)		156DAG; A3a; AGRNR; D9Wsu13e; DAG; DG; DNA segment, Chr 9, Wayne State University 13, expressed; MDDGC7; MDDGC9; alpha-dystroglycan; beta-dystroglycan; dystrophin associated glycoprotein 1;
General Note		Phenotypic Similarity to Human Syndrome: Type II (cobblestone) Lissencephaly (J:86901). Phenotypic Similarity to Human Syndrome: Cardiomyopathy, Dilated (J:169951).
Molecular Note		Exon 2 was floxed by introducing a loxP site downstream of exon 2 and by inserting a floxed neo cassette into the upstream intron via homologous recombination. [MGI Ref ID J:78838]

Genotyping

Genotyping Information

Genotyping Protocols

Dag1^tm2Kcam, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Cohn RD; Henry MD; Michele DE; Barresi R; Saito F; Moore SA; Flanagan JD; Skwarchuk MW; Robbins ME; Mendell JR; Williamson RA; Campbell KP. 2002. Disruption of DAG1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration. Cell 110(5):639-48. [PubMed: 12230980]  [MGI Ref ID J:78838]

Additional References

Dag1^tm2Kcam related

Beedle AM; Nienaber PM; Campbell KP. 2007. Fukutin-related protein associates with the sarcolemmal dystrophin-glycoprotein complex. J Biol Chem 282(23):16713-7. [PubMed: 17452335]  [MGI Ref ID J:122734]

Berti C; Bartesaghi L; Ghidinelli M; Zambroni D; Figlia G; Chen ZL; Quattrini A; Wrabetz L; Feltri ML. 2011. Non-redundant function of dystroglycan and beta1 integrins in radial sorting of axons. Development 138(18):4025-37. [PubMed: 21862561]  [MGI Ref ID J:176243]

Court FA; Hewitt JE; Davies K; Patton BL; Uncini A; Wrabetz L; Feltri ML. 2009. A laminin-2, dystroglycan, utrophin axis is required for compartmentalization and elongation of myelin segments. J Neurosci 29(12):3908-19. [PubMed: 19321787]  [MGI Ref ID J:147273]

Court FA; Zambroni D; Pavoni E; Colombelli C; Baragli C; Figlia G; Sorokin L; Ching W; Salzer JL; Wrabetz L; Feltri ML. 2011. MMP2-9 cleavage of dystroglycan alters the size and molecular composition of Schwann cell domains. J Neurosci 31(34):12208-17. [PubMed: 21865464]  [MGI Ref ID J:176237]

Dacci P; Dina G; Cerri F; Previtali SC; Lopez ID; Lauria G; Feltri ML; Bolino A; Comi G; Wrabetz L; Quattrini A. 2010. Foot pad skin biopsy in mouse models of hereditary neuropathy. Glia 58(16):2005-16. [PubMed: 20878767]  [MGI Ref ID J:167389]

Han R; Kanagawa M; Yoshida-Moriguchi T; Rader EP; Ng RA; Michele DE; Muirhead DE; Kunz S; Moore SA; Iannaccone ST; Miyake K; McNeil PL; Mayer U; Oldstone MB; Faulkner JA; Campbell KP. 2009. Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of alpha-dystroglycan. Proc Natl Acad Sci U S A 106(31):12573-9. [PubMed: 19633189]  [MGI Ref ID J:152005]

Hu H; Li J; Zhang Z; Yu M. 2011. Pikachurin interaction with dystroglycan is diminished by defective O-mannosyl glycosylation in congenital muscular dystrophy models and rescued by LARGE overexpression. Neurosci Lett 489(1):10-5. [PubMed: 21129441]  [MGI Ref ID J:168704]

Jarad G; Miner JH. 2009. The Pax3-Cre transgene exhibits a rostrocaudal gradient of expression in the skeletal muscle lineage. Genesis 47(1):1-6. [PubMed: 18942111]  [MGI Ref ID J:144640]

Leonoudakis D; Singh M; Mohajer R; Mohajer P; Fata JE; Campbell KP; Muschler JL. 2010. Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity. J Cell Sci 123(Pt 21):3683-92. [PubMed: 20940259]  [MGI Ref ID J:182923]

Levi S; Grady RM; Henry MD; Campbell KP; Sanes JR; Craig AM. 2002. Dystroglycan is selectively associated with inhibitory GABAergic synapses but is dispensable for their differentiation. J Neurosci 22(11):4274-85. [PubMed: 12040032]  [MGI Ref ID J:125567]

Liou LY; Walsh KB; Vartanian AR; Beltran-Valero de Bernabe D; Welch M; Campbell KP; Oldstone MB; Kunz S. 2010. Functional glycosylation of dystroglycan is crucial for thymocyte development in the mouse. PLoS One 5(3):e9915. [PubMed: 20369005]  [MGI Ref ID J:158951]

Michele DE; Kabaeva Z; Davis SL; Weiss RM; Campbell KP. 2009. Dystroglycan matrix receptor function in cardiac myocytes is important for limiting activity-induced myocardial damage. Circ Res 105(10):984-93. [PubMed: 19797173]  [MGI Ref ID J:169951]

Moore SA; Saito F; Chen J; Michele DE; Henry MD; Messing A; Cohn RD; Ross-Barta SE; Westra S; Williamson RA; Hoshi T; Campbell KP. 2002. Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature 418(6896):422-5. [PubMed: 12140559]  [MGI Ref ID J:86901]

Nishimune H; Valdez G; Jarad G; Moulson CL; Muller U; Miner JH; Sanes JR. 2008. Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction. J Cell Biol 182(6):1201-15. [PubMed: 18794334]  [MGI Ref ID J:142595]

Nodari A; Previtali SC; Dati G; Occhi S; Court FA; Colombelli C; Zambroni D; Dina G; Del Carro U; Campbell KP; Quattrini A; Wrabetz L; Feltri ML. 2008. Alpha6beta4 integrin and dystroglycan cooperate to stabilize the myelin sheath. J Neurosci 28(26):6714-9. [PubMed: 18579745]  [MGI Ref ID J:137852]

Noell S; Wolburg-Buchholz K; Mack AF; Beedle AM; Satz JS; Campbell KP; Wolburg H; Fallier-Becker P. 2011. Evidence for a role of dystroglycan regulating the membrane architecture of astroglial endfeet. Eur J Neurosci 33(12):2179-86. [PubMed: 21501259]  [MGI Ref ID J:176372]

Occhi S; Zambroni D; Del Carro U; Amadio S; Sirkowski EE; Scherer SS; Campbell KP; Moore SA; Chen ZL; Strickland S; Di Muzio A; Uncini A; Wrabetz L; Feltri ML. 2005. Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of ranvier. J Neurosci 25(41):9418-27. [PubMed: 16221851]  [MGI Ref ID J:101621]

Omori Y; Araki F; Chaya T; Kajimura N; Irie S; Terada K; Muranishi Y; Tsujii T; Ueno S; Koyasu T; Tamaki Y; Kondo M; Amano S; Furukawa T. 2012. Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells. J Neurosci 32(18):6126-37. [PubMed: 22553019]  [MGI Ref ID J:184863]

Pawlisz AS; Feng Y. 2011. Three-dimensional regulation of radial glial functions by Lis1-Nde1 and dystrophin glycoprotein complexes. PLoS Biol 9(10):e1001172. [PubMed: 22028625]  [MGI Ref ID J:184033]

Saito F; Moore SA; Barresi R; Henry MD; Messing A; Ross-Barta SE; Cohn RD; Williamson RA; Sluka KA; Sherman DL; Brophy PJ; Schmelzer JD; Low PA; Wrabetz L; Feltri ML; Campbell KP. 2003. Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and sodium channel stabilization. Neuron 38(5):747-58. [PubMed: 12797959]  [MGI Ref ID J:83782]

Satz JS; Ostendorf AP; Hou S; Turner A; Kusano H; Lee JC; Turk R; Nguyen H; Ross-Barta SE; Westra S; Hoshi T; Moore SA; Campbell KP. 2010. Distinct functions of glial and neuronal dystroglycan in the developing and adult mouse brain. J Neurosci 30(43):14560-72. [PubMed: 20980614]  [MGI Ref ID J:166208]

Satz JS; Philp AR; Nguyen H; Kusano H; Lee J; Turk R; Riker MJ; Hernandez J; Weiss RM; Anderson MG; Mullins RF; Moore SA; Stone EM; Campbell KP. 2009. Visual impairment in the absence of dystroglycan. J Neurosci 29(42):13136-46. [PubMed: 19846701]  [MGI Ref ID J:158199]

Stalnaker SH; Aoki K; Lim JM; Porterfield M; Liu M; Satz JS; Buskirk S; Xiong Y; Zhang P; Campbell KP; Hu H; Live D; Tiemeyer M; Wells L. 2011. Glycomic analyses of mouse models of congenital muscular dystrophy. J Biol Chem 286(24):21180-90. [PubMed: 21460210]  [MGI Ref ID J:173659]

Weir ML; Oppizzi ML; Henry MD; Onishi A; Campbell KP; Bissell MJ; Muschler JL. 2006. Dystroglycan loss disrupts polarity and {beta}-casein induction in mammary epithelial cells by perturbing laminin anchoring. J Cell Sci 119(Pt 19):4047-58. [PubMed: 16968749]  [MGI Ref ID J:113187]

Zhang Z; Zhang P; Hu H. 2011. LARGE Expression Augments the Glycosylation of Glycoproteins in Addition to alpha-Dystroglycan Conferring Laminin Binding. PLoS One 6(4):e19080. [PubMed: 21533062]  [MGI Ref ID J:172396]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

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.

Payment Terms and Conditions

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.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

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

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.