Description

Strain Information

Former Names STOCK rd8    (Changed: 15-DEC-04 ) Type Mutant Stock; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   01-MAR-06 Species laboratory mouse Generation N3F12+ (09-OCT-03) Generation Definitions

Appearance
black
Related Genotype: a/a

Important Note
The C57BL/6J background strain is homozygous for the age related hearing loss mutation Cdh23^ahl, which on this background results in progressive hearing loss with onset after 10 months of age.

Development
The Cat^b (catalase 1 null) mutation was identified in a screen for low catalase activity by Feinstein et al. (1964, 1966) at Argonne National Laboratory of offpring of (C3H x 101) male mice irradiated at Oak Ridge National Laboratory (600 R in fractionated exposures), then crossed to females of the Oak Ridge "multiple recessive testing stock" derived from a cross of NB mice (aabbc^ch p/c^ch p d se/d se) and mice of a non-inbred stock homozygous for three of the same recessive mutations, as well as for s, from which mice homozygous for all seven mutations were bred and maintained afterward by random breeding (Russell 1951). Putative heterozygotes for catalase deficiency were crossed to normal mice (not clearly identified, but presumably unirradiated progeny of (101 x C3H)F1 X ORNL testing stock), and offspring exhibiting low catalase activity were backcrossed to the heterozygous parent (Feinstein et al. 1966).Cat^b was subsequently transferred by backcrossing for eight generations onto C3H/HeAnl, a line carrying mouse mammary tumor virus (MMTV) and another line (C3Hf) free of the virus (Feinstein et al. 1978). The Jackson Laboratory received C3HfB/Ga-Cat^b from Allen H. Gates, then at the University of Rochester, in 1982.

Although all C3H strains carry the rd1 (retinal degeneration 1) mutation at Pde6b, the gene encoding the beta subunit of phosphodiesterase 1, retinas of these mice exhibited a peculiar, granular appearance distinct from the usual Pde6b^rd1 phenotype. F2 progeny of a cross of C3HfB/Ga-Cat^b and C57BL/6J mice exhibited three retinal phenotypes: 1) normal; 2) patches of pigment deposition and large, diffuse pigmented regions typical Pde6b^rd1 homozygotes; and 3) small, discrete, light-colored dots throughout the fundus. Mice exhibiting the last phenotype were intercrossed among themselves to produce a stock homozygous for Mfrp^rd6 and for the wild-type allele at Pde6b. During this process, a separate mutation with a distinct map position was identified and characterized as Crb1^rd8. STOCK Crb1^rd8 Mfrp^rd6/J (stock #004299) is homozygous for both Mfrp^rd6 and Crb1^rd8 on this mixed genetic background that derived in part from C57BL/6J, C3H, 101, and a linkage testing stock derived from non-inbred stocks. In order to isolate Mfrp^rd6 and Crb1^rd8 this strain was backcrossed to C57BL/6J, and selection for either Mfrp^rd6 or Crb1^rd8 yielded B6.C3Ga-Mfrp^rd6/J (stock #003684) and STOCK Crb1^rd8/J (stock #003392) respectively.

Control Information

	Control
	See control note:	C57BL/6J (Stock Number 000664) is only an approximate control for this stock, whose genetic background is ~87.5% C57BL/6J and ~12.5% C3HfB/Ga.
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Cdh23^ahl allele

001137	129P1/ReJ
000690	129P3/J
000691	129X1/SvJ
000646	A/J
000647	A/WySnJ
003070	ALR/LtJ
003072	ALS/LtJ
004502	B6;AKR-Lxl2/GrsrJ
001026	BALB/cByJ
000653	BUB/BnJ
005494	C3.129S1(B6)-Grm1rcw/J
000664	C57BL/6J
004764	C57BL/6J-Cdh23v-8J/J
003129	C57BL/6J-Epha4rb-2J/GrsrJ
004820	C57BL/6J-Kcne12J/J
004703	C57BL/6J-Kcnq2Nmf134/J
004811	C57BL/6J-nmf110/J
004812	C57BL/6J-nmf111/J
004747	C57BL/6J-nmf118/J
004656	C57BL/6J-nmf88/J
004391	C57BL/6J-Chr 13A/J/NaJ
004385	C57BL/6J-Chr 7A/J/NaJ
000662	C57BLKS/J
000667	C57BR/cdJ
000668	C57L/J
000669	C58/J
010614	CBACa.B6-Cdh23ahl/Kjn
000657	CE/J
000670	DBA/1J
001140	DBA/1LacJ
000671	DBA/2J
007048	DBA/2J-Gpnmb+/SjJ
002106	KK/HlJ
000675	LG/J
000676	LP/J
000677	MA/MyJ
001976	NOD/ShiLtJ
002050	NOR/LtJ
000679	P/J
002747	SENCARB/PtJ
002335	SKH2/J

View Strains carrying   Cdh23^ahl     (41 strains)

Strains carrying   Crb1^rd8 allele

005711	B6.129P2-Prkcqtm1Litt/J
004852	B6;129-Crb1rd8/J

View Strains carrying   Crb1^rd8     (2 strains)

Strains carrying other alleles of Cdh23

001137	129P1/ReJ
000690	129P3/J
000691	129X1/SvJ
000646	A/J
000647	A/WySnJ
003070	ALR/LtJ
003072	ALS/LtJ
002552	B6(V)-Cdh23v-2J/J
002756	B6.CAST-Cdh23Ahl+/Kjn
010615	B6.CBACa-Cdh23CBA/CaJ/Kjn
004502	B6;AKR-Lxl2/GrsrJ
002432	B6J x B6.C-H2-Kbm1/ByJ-Cdh23v-J/J
001026	BALB/cByJ
000653	BUB/BnJ
005494	C3.129S1(B6)-Grm1rcw/J
000664	C57BL/6J
004764	C57BL/6J-Cdh23v-8J/J
004819	C57BL/6J-Cdh23v-9J/J
003129	C57BL/6J-Epha4rb-2J/GrsrJ
004820	C57BL/6J-Kcne12J/J
004703	C57BL/6J-Kcnq2Nmf134/J
004811	C57BL/6J-nmf110/J
004812	C57BL/6J-nmf111/J
004747	C57BL/6J-nmf118/J
004656	C57BL/6J-nmf88/J
004391	C57BL/6J-Chr 13A/J/NaJ
004385	C57BL/6J-Chr 7A/J/NaJ
000662	C57BLKS/J
000667	C57BR/cdJ
000668	C57L/J
000669	C58/J
010614	CBACa.B6-Cdh23ahl/Kjn
005016	CByJ;B6-Cdh23v-10J/J
000657	CE/J
000670	DBA/1J
001140	DBA/1LacJ
000671	DBA/2J
007048	DBA/2J-Gpnmb+/SjJ
002106	KK/HlJ
000675	LG/J
000676	LP/J
000677	MA/MyJ
001976	NOD/ShiLtJ
002050	NOR/LtJ
000679	P/J
002747	SENCARB/PtJ
002335	SKH2/J
000275	V/LeJ

View Strains carrying other alleles of Cdh23     (48 strains)

Strains carrying other alleles of Crb1

005711	B6.129P2-Prkcqtm1Litt/J
004852	B6;129-Crb1rd8/J

View Strains carrying other alleles of Crb1     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Leber Congenital Amaurosis 8; LCA8 5

5 Conditionally targeted allele(s)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Crb1^rd8/Crb1^rd8

        STOCK Crb1^rd8/J

• vision/eye phenotype
• abnormal ocular fundus morphology
  • mice exhibit large, irregularly shaped spots concentrated in the inferior nasal quadrant of the fundus as early as week 3 that correspond to retinal folds and pseudorosettes   (MGI Ref ID J:85459)
• • abnormal retina morphology
    • retinal thinning in both the inner and outer segment is observed   (MGI Ref ID J:85459)
  • • abnormal Muller cell morphology
      • Muller cells exhibit increased electron density and cytoplasmic strands that are more easily traced through the plexiform layer than in wild-type mice   (MGI Ref ID J:85459)
    • abnormal retina outer limiting membrane morphology
      • the external limiting membrane in the retina is fragmented and disorganized at 2 weeks and is more severe at 4 weeks   (MGI Ref ID J:85459)
    • abnormal retinal photoreceptor morphology
      • the photoreceptor lamellae breaks down   (MGI Ref ID J:85459)
    • • abnormal photoreceptor inner segment morphology
        • the photoreceptor inner segments lose their orderly arrangement   (MGI Ref ID J:85459)
        • by 5 months the inner segment approaches the retinal pigment epithelium   (MGI Ref ID J:85459)
        • swelling occurs in portions of the inner segments   (MGI Ref ID J:85459)
      • • short photoreceptor inner segment
          • at 4 weeks the photoreceptor inner segments are 25% shorter   (MGI Ref ID J:85459)
      • decreased retinal photoreceptor cell number
        • in the region of focal degeneration photoreceptors are lost   (MGI Ref ID J:85459)
      • photoreceptor outer segment degeneration
        • by week 10 the outer segment begins to fragment   (MGI Ref ID J:85459)
        • by 5 months only a few outer segment fragments remain   (MGI Ref ID J:85459)
      • short photoreceptor outer segment
        • the photoreceptor outer segments are shortened   (MGI Ref ID J:85459)
    • thin retinal outer nuclear layer
      • in older mice, the retinal outer nuclear layer is reduced to a single row of nuclei   (MGI Ref ID J:85459)
• nervous system phenotype
• abnormal Muller cell morphology
  • Muller cells exhibit increased electron density and cytoplasmic strands that are more easily traced through the plexiform layer than in wild-type mice   (MGI Ref ID J:85459)
• abnormal retinal photoreceptor morphology
  • the photoreceptor lamellae breaks down   (MGI Ref ID J:85459)
• • abnormal photoreceptor inner segment morphology
    • the photoreceptor inner segments lose their orderly arrangement   (MGI Ref ID J:85459)
    • by 5 months the inner segment approaches the retinal pigment epithelium   (MGI Ref ID J:85459)
    • swelling occurs in portions of the inner segments   (MGI Ref ID J:85459)
  • • short photoreceptor inner segment
      • at 4 weeks the photoreceptor inner segments are 25% shorter   (MGI Ref ID J:85459)
  • decreased retinal photoreceptor cell number
    • in the region of focal degeneration photoreceptors are lost   (MGI Ref ID J:85459)
  • photoreceptor outer segment degeneration
    • by week 10 the outer segment begins to fragment   (MGI Ref ID J:85459)
    • by 5 months only a few outer segment fragments remain   (MGI Ref ID J:85459)
  • short photoreceptor outer segment
    • the photoreceptor outer segments are shortened   (MGI Ref ID J:85459)

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

Crb1^rd8/Crb1^rd8

        involves: C3HfB6/Ga * C57BL/6 * CAST/EiJ

• vision/eye phenotype
• abnormal retina morphology
  • 19% of mice do not display the spotting phenotype on a CAST/EiJ mixed background   (MGI Ref ID J:85459)

Crb1^rd8/Crb1^rd8

        B6.Cg-Crb1^rd8

• vision/eye phenotype
• *normal* vision/eye phenotype
  • mice no longer display the spotting phenotype when backcrossed from a CAST/EiJ background onto a C57BL/6 background   (MGI Ref ID J:85459)

View Research Applications

Research Applications

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

Cdh23^ahl related

Neurobiology Research
Hearing Defects
      Age related hearing loss

Sensorineural Research
Hearing Defects
      Age related hearing loss

Crb1^rd8 related

Cell Biology Research
Defects in Cell Adhesion Molecules

Developmental Biology Research
Eye Defects

Mouse/Human Gene Homologs
Retinitis pigmentosa 12; Leber congenital amaurosis (CLA)

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Crb1rd8
Allele Name		retinal degeneration 8
Allele Type		Spontaneous
Common Name(s)		nmf144;
Strain of Origin		C57BL/6J
Gene Symbol and Name		Crb1, crumbs homolog 1 (Drosophila)
Chromosome		1
Gene Common Name(s)		7530426H14Rik; A930008G09Rik; LCA8; RIKEN cDNA 7530426H14 gene; RIKEN cDNA A930008G09 gene; RP12;
Molecular Note		The mutation in the rd8 mouse has been identified as a single base deletion in the Crb1 gene. This deletion causes a frame shift and a premature stop codon that truncates the transmembrane and cytoplasmic domain of the protein. [MGI Ref ID J:85459]
Allele Symbol		Cdh23ahl
Allele Name		age related hearing loss 1
Allele Type		QTL
Common Name(s)		Cdh23753A; mdfw;
Strain of Origin		multiple strains
Gene Symbol and Name		Cdh23, cadherin 23 (otocadherin)
Chromosome		10
Gene Common Name(s)		4930542A03Rik; CDHR23; RIKEN cDNA 4930542A03 gene; USH1D; W; age related hearing loss 1; ahl; bob; bobby; bus; bustling; mdfw; modifier of deaf waddler; neuroscience mutagenesis facility, 112; neuroscience mutagenesis facility, 181; neuroscience mutagenesis facility, 252; nmf112; nmf181; nmf252; sals; salsa; v; waltzer;
Molecular Note		Genetic complementation tests have shown allelism between the mdfw (modifier of deaf waddler) locus and the ahl locus. Further analysis has identified an association between ahl and a G to A transition at nucleotide position 753 of Cdh23. This hypomorphic allele causes in frame skipping of exon 7 and reduced message stability. Twenty-seven strains classified with ahl and carrying the 753A allele include: CD1, RBF/DnJ, PL/J, AKR/J, RF/J, BALB/cBy, A/WySnJ, P/J, SENCARA/PtJ, DBA/1J, ALS/LtJ, C58/J, C57BLKS/J, 129P1/ReJ, C57BR/cd, SKH2/J, BUB/Bn, MA/MyJ, LP/J, 129X1/SvJ, NOR/LtJ, A/J, C57BL/6, NOD/LtJ, DBA/2J, ALR/LtJ, C57L/J. Strains classified with ahl that DO NOT carry this mutation include: C3H/HeSnJ, I/LnJ,YBR/Ei, MRL/MpJ. [MGI Ref ID J:86905]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Mehalow AK; Kameya S; Smith RS; Hawes NL; Denegre JM; Young JA; Bechtold L; Haider NB; Tepass U; Heckenlively JR; Chang B; Naggert JK; Nishina PM. 2003. CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Hum Mol Genet 12(17):2179-89. [PubMed: 12915475]  [MGI Ref ID J:85459]

Additional References

Cdh23^ahl related

Davis RR; Newlander JK; Ling X; Cortopassi GA; Krieg EF; Erway LC. 2001. Genetic basis for susceptibility to noise-induced hearing loss in mice. Hear Res 155(1-2):82-90. [PubMed: 11335078]  [MGI Ref ID J:69679]

Di Palma F; Pellegrino R; Noben-Trauth K. 2001. Genomic structure, alternative splice forms and normal and mutant alleles of cadherin 23 (Cdh23). Gene 281(1-2):31-41. [PubMed: 11750125]  [MGI Ref ID J:73941]

Han F; Yu H; Tian C; Chen HE; Benedict-Alderfer C; Zheng Y; Wang Q; Han X; Zheng QY. 2010. A new mouse mutant of the Cdh23 gene with early-onset hearing loss facilitates evaluation of otoprotection drugs. Pharmacogenomics J :. [PubMed: 20644563]  [MGI Ref ID J:174758]

Johnson KR; Erway LC; Cook SA; Willott JF; Zheng QY. 1997. A major gene affecting age-related hearing loss in C57BL/6J mice Hear Res 114(1-2):83-92. [PubMed: 9447922]  [MGI Ref ID J:44966]

Johnson KR; Longo-Guess C; Gagnon LH; Yu H; Zheng QY. 2008. A locus on distal chromosome 11 (ahl8) and its interaction with Cdh23 ahl underlie the early onset, age-related hearing loss of DBA/2J mice. Genomics 92(4):219-25. [PubMed: 18662770]  [MGI Ref ID J:139223]

Johnson KR; Yu H; Ding D; Jiang H; Gagnon LH; Salvi RJ. 2010. Separate and combined effects of Sod1 and Cdh23 mutations on age-related hearing loss and cochlear pathology in C57BL/6J mice. Hear Res 268(1-2):85-92. [PubMed: 20470874]  [MGI Ref ID J:163035]

Johnson KR; Zheng QY; Bykhovskaya Y; Spirina O; Fischel-Ghodsian N. 2001. A nuclear-mitochondrial DNA interaction affecting hearing impairment in mice. Nat Genet 27(2):191-4. [PubMed: 11175788]  [MGI Ref ID J:67312]

Johnson KR; Zheng QY; Noben-Trauth K. 2006. Strain background effects and genetic modifiers of hearing in mice. Brain Res 1091(1):79-88. [PubMed: 16579977]  [MGI Ref ID J:110459]

Johnson KR; Zheng QY; Weston MD; Ptacek LJ; Noben-Trauth K. 2005. The Mass1(frings) mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC. Genomics 85(5):582-90. [PubMed: 15820310]  [MGI Ref ID J:97534]

Keithley EM; Canto C; Zheng QY; Fischel-Ghodsian N; Johnson KR. 2004. Age-related hearing loss and the ahl locus in mice. Hear Res 188(1-2):21-8. [PubMed: 14759567]  [MGI Ref ID J:87783]

Liu X; Bulgakov OV; Darrow KN; Pawlyk B; Adamian M; Liberman MC; Li T. 2007. Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells. Proc Natl Acad Sci U S A 104(11):4413-8. [PubMed: 17360538]  [MGI Ref ID J:118927]

Manji SS; Williams LH; Miller KA; Ooms LM; Bahlo M; Mitchell CA; Dahl HH. 2011. A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart. PLoS One 6(3):e17607. [PubMed: 21423608]  [MGI Ref ID J:171701]

Mathews CE; Leiter EH. 1999. Resistance of ALR/Lt islets to free radical-mediated diabetogenic stress is inherited as a dominant trait. Diabetes 48(11):2189-96. [PubMed: 10535453]  [MGI Ref ID J:109893]

Nadeau JH. 2003. Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 13(3):290-5. [PubMed: 12787792]  [MGI Ref ID J:88012]

Noben-Trauth K; Latoche JR; Neely HR; Bennett B. 2010. Phenotype and genetics of progressive sensorineural hearing loss (Snhl1) in the LXS set of recombinant inbred strains of mice. PLoS One 5(7):e11459. [PubMed: 20628639]  [MGI Ref ID J:163117]

Noben-Trauth K; Zheng QY; Johnson KR. 2003. Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss. Nat Genet 35(1):21-3. [PubMed: 12910270]  [MGI Ref ID J:86905]

Noben-Trauth K; Zheng QY; Johnson KR; Nishina PM. 1997. mdfw: a deafness susceptibility locus that interacts with deaf waddler (dfw). Genomics 44(3):266-72. [PubMed: 9325047]  [MGI Ref ID J:38429]

Perrin BJ; Sonnemann KJ; Ervasti JM. 2010. beta-actin and gamma-actin are each dispensable for auditory hair cell development but required for Stereocilia maintenance. PLoS Genet 6(10):e1001158. [PubMed: 20976199]  [MGI Ref ID J:167543]

Vazquez AE; Jimenez AM; Martin GK; Luebke AE; Lonsbury-Martin BL. 2004. Evaluating cochlear function and the effects of noise exposure in the B6.CAST+Ahl mouse with distortion product otoacoustic emissions. Hear Res 194(1-2):87-96. [PubMed: 15276680]  [MGI Ref ID J:117746]

Zheng QY; Johnson KR. 2001. Hearing loss associated with the modifier of deaf waddler (mdfw) locus corresponds with age-related hearing loss in 12 inbred strains of mice. Hear Res 154(1-2):45-53. [PubMed: 11423214]  [MGI Ref ID J:70964]

Zilberstein Y; Liberman MC; Corfas G. 2012. Inner hair cells are not required for survival of spiral ganglion neurons in the adult cochlea. J Neurosci 32(2):405-10. [PubMed: 22238076]  [MGI Ref ID J:179911]

Crb1^rd8 related

Chang B; Hawes NL; Hurd RE; Davisson MT; Nusinowitz S; Heckenlively JR. 2002. Retinal degeneration mutants in the mouse. Vision Res 42(4):517-25. [PubMed: 11853768]  [MGI Ref ID J:75095]

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 Ref ID J:156373]

Lakowski J; Baron M; Bainbridge J; Barber AC; Pearson RA; Ali RR; Sowden JC. 2010. Cone and rod photoreceptor transplantation in models of the childhood retinopathy Leber congenital amaurosis using flow-sorted Crx-positive donor cells. Hum Mol Genet :. [PubMed: 20858907]  [MGI Ref ID J:165574]

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 Ref ID J:166679]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           A1

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Eye Mutant Resource within the Mouse Mutant Resource collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	See control note:	C57BL/6J (Stock Number 000664) is only an approximate control for this stock, whose genetic background is ~87.5% C57BL/6J and ~12.5% C3HfB/Ga.
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Important Note

The C57BL/6J background strain is homozygous for the age related hearing loss mutation Cdh23^ahl, which on this background results in progressive hearing loss with onset after 10 months of age.

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.

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