Strain Name:

B6N.129P2-Dazltm1Hjc/J

Stock Number:

023802

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Availability:

Repository- Live

These mice carry a targeted knockout of Dazl (deleted in azoospermia-like) on the C57BL/6N genetic background. Homozygotes are infertile, but otherwise healthy. Germ cells fail to activate genes required for both male-specific and female-specific sexual differentiation in homozygous knockout mice. This phenotype appears to be sensitive to the genetic background.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemWild-type x Heterozygote         (Female x Male)   22-JAN-14
Mating SystemHeterozygote x Wild-type         (Female x Male)   22-JAN-14
Specieslaboratory mouse
GenerationN27+pN1 (28-FEB-14)
Generation Definitions
 
Donating Investigator David Page,   Whitehead Institute for Biomedical Research

Description
Dazl (deleted in azoospermia-like) is a germ cell-specific RNA binding protein that is expressed in post-migratory primordial germ cells as well as postnatal germ cells. On the C57BL/6N genetic background, it acts as a competence factor for gametogenesis.

These mice carry a targeted knockout of Dazl on the C57BL/6N genetic background. RT-PCR confirms the absence of transcript and western blot/immunohistochemistry fail to detect any protein generated from the null allele. Heterozygotes are viable and fertile. Homozygotes are infertile, but otherwise healthy. Germ cells fail to activate genes required for both male-specific and female-specific sexual differentiation in homozygous knockout mice. Post migratory germ cells retain PGC-like gene expression and eventually die. This phenotype appears to be sensitive to strain background, however.

Development
Exons 6 and 7, and all but five amino acids of exon 5 were replaced by a neomycin resistance cassette via homologous recombination in 129P2/OlaHsd-derived CGR8 embryonic stem (ES) cells. This strain was originally maintained on an outbred MF1 genetic background in Howard Cooke's laboratory, but has since been backcrossed to C57BL/6NTac by the donating laboratory for more than 27 generations. Upon arrival at The Jackson Laboratory, this line was re-derived with C57BL/6NJ (see Stock No. 005304). All Y chromosomes and mitochondria are of C57BL/6 origin.

Control Information

  Control
   Wild-type from the colony
   005304 C57BL/6NJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Dazl
007732   B6SJL-Tg(Dazl-hrGFP)4Gar/J
009354   FVB/N-Tg(Dazl-EGFP)10Rarp/J
View Strains carrying other alleles of Dazl     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Dazltm1Hjc/Dazl+

        involves: 129P2/OlaHsd * MF1
  • reproductive system phenotype
  • abnormal male germ cell morphology
    • 60% of sperm are visibly abnormal   (MGI Ref ID J:42612)
    • oligozoospermia
      • reduced amount of epididymal sperm   (MGI Ref ID J:42612)

Dazltm1Hjc/Dazltm1Hjc

        involves: 129P2/OlaHsd * MF1
  • endocrine/exocrine gland phenotype
  • abnormal seminiferous tubule morphology
    • reduced tubule diameter relative to wild-type   (MGI Ref ID J:71070)
    • fewer tubules per cross-section   (MGI Ref ID J:42612)
  • absent ovarian follicles
    • neither follicles nor ova were observed   (MGI Ref ID J:42612)
  • small ovary   (MGI Ref ID J:42612)
  • small testis
    • 3-fold reduction in testis mass relative to wild-type littermates   (MGI Ref ID J:42612)
  • reproductive system phenotype
  • abnormal seminiferous tubule morphology
    • reduced tubule diameter relative to wild-type   (MGI Ref ID J:71070)
    • fewer tubules per cross-section   (MGI Ref ID J:42612)
  • absent ovarian follicles
    • neither follicles nor ova were observed   (MGI Ref ID J:42612)
  • arrest of spermatogenesis   (MGI Ref ID J:42612)
    • spermatogonia were contained within 76% of adult tubules   (MGI Ref ID J:71070)
    • spermatocytes were contained within 3% of adult tubules   (MGI Ref ID J:71070)
    • failure of A aligned spermatogonia to differentiate into A1 spermatogonia   (MGI Ref ID J:71070)
  • female infertility   (MGI Ref ID J:42612)
  • male infertility   (MGI Ref ID J:42612)
  • small ovary   (MGI Ref ID J:42612)
  • small testis
    • 3-fold reduction in testis mass relative to wild-type littermates   (MGI Ref ID J:42612)
View Research Applications

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

Cell Biology Research
Cell Cycle Regulation

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Dazltm1Hjc
Allele Name targeted mutation 1, Howard J Cooke
Allele Type Targeted (Null/Knockout)
Common Name(s) Dazl-; DazlaTm1Hgu; Dazlko; dazlTm1hgu;
Strain of Origin129P2/OlaHsd
Gene Symbol and Name Dazl, deleted in azoospermia-like
Chromosome 17
Gene Common Name(s) DAZ-like autosomal; Daz-like; Dazla; Tpx-2; Tpx2; pDP1678; testis specific gene 2;
Molecular Note Exons 5 through 7 were disrupted by the insertion of a neomycin selection cassette. Mutant transcripts were undetected via RT-PCR analysis of total RNA isolated from heterozygous mice. Western blot analysis of testis extracts showed an absence of proteinin homozygous mutant mice. [MGI Ref ID J:42612]

Genotyping

Genotyping Information

Genotyping Protocols

Dazltm1Hjc,

MELT



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Ruggiu M; Speed R; Taggart M; McKay SJ; Kilanowski F; Saunders P ; Dorin J ; Cooke HJ. 1997. The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 389(6646):73-7. [PubMed: 9288969]  [MGI Ref ID J:42612]

Additional References

Dazltm1Hjc related

Cooke HJ; Saunders PT. 2002. Mouse models of male infertility. Nat Rev Genet 3(10):790-801. [PubMed: 12360237]  [MGI Ref ID J:79958]

Gill ME; Hu YC; Lin Y; Page DC. 2011. Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells. Proc Natl Acad Sci U S A 108(18):7443-8. [PubMed: 21504946]  [MGI Ref ID J:172213]

Grootegoed JA; Baarends WM; Roest HP; Hoeijmakers JH. 1998. Knockout mouse model and gametogenic failure. Mol Cell Endocrinol 145(1-2):161-6. [PubMed: 9922113]  [MGI Ref ID J:52347]

Haston KM; Tung JY; Reijo Pera RA. 2009. Dazl functions in maintenance of pluripotency and genetic and epigenetic programs of differentiation in mouse primordial germ cells in vivo and in vitro. PLoS ONE 4(5):e5654. [PubMed: 19468308]  [MGI Ref ID J:148836]

Jiao X; Trifillis P; Kiledjian M. 2002. Identification of Target Messenger RNA Substrates for the Murine Deleted in Azoospermia-Like RNA-Binding Protein. Biol Reprod 66(2):475-85. [PubMed: 11804965]  [MGI Ref ID J:74010]

Kim B; Cooke HJ; Rhee K. 2012. DAZL is essential for stress granule formation implicated in germ cell survival upon heat stress. Development 139(3):568-78. [PubMed: 22223682]  [MGI Ref ID J:179729]

Lin Y; Gill ME; Koubova J; Page DC. 2008. Germ cell-intrinsic and -extrinsic factors govern meiotic initiation in mouse embryos. Science 322(5908):1685-7. [PubMed: 19074348]  [MGI Ref ID J:142245]

Lin Y; Page DC. 2005. Dazl deficiency leads to embryonic arrest of germ cell development in XY C57BL/6 mice. Dev Biol 288(2):309-16. [PubMed: 16310179]  [MGI Ref ID J:104848]

Maratou K; Forster T; Costa Y; Taggart M; Speed RM; Ireland J; Teague P; Roy D; Cooke HJ. 2004. Expression profiling of the developing testis in wild-type and Dazl knockout mice. Mol Reprod Dev 67(1):26-54. [PubMed: 14648873]  [MGI Ref ID J:109709]

McNeilly JR; Saunders PT; Taggart M; Cranfield M; Cooke HJ; McNeilly AS. 2000. Loss of oocytes in Dazl knockout mice results in maintained ovarian steroidogenic function but altered gonadotropin secretion in adult animals Endocrinology 141(11):4284-94. [PubMed: 11089564]  [MGI Ref ID J:65576]

McNeilly JR; Watson EA; White YA; Murray AA; Spears N; McNeilly AS. 2011. Decreased oocyte DAZL expression in mice results in increased litter size by modulating follicle-stimulating hormone-induced follicular growth. Biol Reprod 85(3):584-93. [PubMed: 21270429]  [MGI Ref ID J:176706]

Naz RK; Rajesh C. 2005. Gene knockouts that cause female infertility: search for novel contraceptive targets Front Biosci 10:2447-2459. [PubMed: 15970507]  [MGI Ref ID J:103183]

R R; Speed R; Taggart M; Cooke HJ. 2003. Spermatogenesis in testes of Dazl null mice after transplantation of wild-type germ cells. Reproduction 126(5):599-604. [PubMed: 14611632]  [MGI Ref ID J:87151]

Reynolds N; Collier B; Bingham V; Gray NK; Cooke HJ. 2007. Translation of the synaptonemal complex component Sycp3 is enhanced in vivo by the germ cell specific regulator Dazl. RNA 13(7):974-81. [PubMed: 17526644]  [MGI Ref ID J:136465]

Saunders PT; Turner JM; Ruggiu M; Taggart M; Burgoyne PS; Elliott D; Cooke HJ. 2003. Absence of mDazl produces a final block on germ cell development at meiosis. Reproduction 126(5):589-97. [PubMed: 14611631]  [MGI Ref ID J:87152]

Schrans-Stassen BH; Saunders PT; Cooke HJ; de Rooij DG. 2001. Nature of the spermatogenic arrest in Dazl -/- mice. Biol Reprod 65(3):771-6. [PubMed: 11514340]  [MGI Ref ID J:71070]

Slee R; Grimes B; Speed RM; Taggart M; Maguire SM; Ross A; McGill NI; Saunders PT; Cooke HJ. 1999. A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype. Proc Natl Acad Sci U S A 96(14):8040-5. [PubMed: 10393944]  [MGI Ref ID J:120235]

Vogel T; Speed RM; Ross A; Cooke HJ. 2002. Partial rescue of the Dazl knockout mouse by the human DAZL gene. Mol Hum Reprod 8(9):797-804. [PubMed: 12200456]  [MGI Ref ID J:102354]

Vogel T; Speed RM; Teague P; Cooke HJ. 1999. Mice with Y chromosome deletion and reduced Rbm genes on a heterozygous Dazl1 null background mimic a human azoospermic factor phenotype. Hum Reprod 14(12):3023-9. [PubMed: 10601091]  [MGI Ref ID J:59032]

Xu EY; Chang R; Salmon NA; Reijo Pera RA. 2007. A gene trap mutation of a murine homolog of the Drosophila stem cell factor Pumilio results in smaller testes but does not affect litter size or fertility. Mol Reprod Dev 74(7):912-21. [PubMed: 17219433]  [MGI Ref ID J:123531]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & HusbandryHeterozygotes are viable and fertile. Some of the males are poor breeders. Homozygotes are infertile, but otherwise healthy.
Mating SystemWild-type x Heterozygote         (Female x Male)   22-JAN-14
Heterozygote x Wild-type         (Female x Male)   22-JAN-14
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Dazltm1Hjc  
Price per Pair (US dollars $)Pair Genotype
$304.00Heterozygous for Dazltm1Hjc x Wild-type for Dazltm1Hjc  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Dazltm1Hjc  
Price per Pair (US dollars $)Pair Genotype
$395.20Heterozygous for Dazltm1Hjc x Wild-type for Dazltm1Hjc  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Wild-type from the colony
   005304 C57BL/6NJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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