Strain Name:

BKS(HRS)-Ddr2slie/JngJ

Stock Number:

008172

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Availability:

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Mice homozygous for the spontaneous mutation smallie (slie) in the Ddr2 (discoidin domain receptor family, member 2) gene appear normal at birth but by weaning they exhibit dwarfism and minor craniofacial abnormalities. Homozygous females lack a corpora lutea by six weeks. By four months, homozygous males exhibit atrophy of spermatogonia, Sertoli and Leydig cells. This mutant mouse strain has characteristics similar to human Levi type dwarfism and may be useful in studies related to dwarfism and infertility.

Description

Strain Information

Type Spontaneous Mutation;
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Mating SystemHeterozygote x Heterozygote         (Female x Male)   11-SEP-08
Specieslaboratory mouse
H2 Haplotyped
GenerationF?+F6 (09-MAR-11)
Generation Definitions

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for this mutation appear normal at birth. By weaning, they exhibit a reduced body mass, gain weight slower and display minor craniofacial abnormalities such as protruding eyes and a shortened snout. Bone mineral content, but not density is reduced in homozygotes. Plasma glucose levels are significantly increased while blood urea nitrogen levels are decreased in homozygotes. By six weeks, it can be seen that homozygous females lack a corpora lutea. By four months, homozygous males exhibit atrophy of spermatogonia, Sertoli and Leydig cells. This mutant mouse strain has characteristics similar to human Levi type dwarfism and may be useful in studies related to dwarfism and infertility.

Development
This recessive mutation arose spontaneously in the BKSChpLt(HRS)-Tg(Ins2-Cpe)1Lt Cpefat/LtJng colony in the laboratory of Dr. Jurgen Naggert, The Jackson Laboratory. Mice homozygous for the mutation are infertile, therefore, a heterozygous sibling was crossed to C57BLKS/J. The colony then was established by sibling mating. The mutations Tg(Ins2-Cpe)1Lt and Cpefat have been selectively bred out.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
Dwarfism, Levi Type 5
5 Conditionally targeted allele(s)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ddr2slie/Ddr2slie

        BKSChpLt.Cg-Tg(Ins2-Cpe)1Lt Cpefat/LtJng
  • mortality/aging
  • decreased survivor rate
    • 15% of homozygotes die before 3 months of age and 47% die by 6 months   (MGI Ref ID J:134371)
  • endocrine/exocrine gland phenotype
  • absent corpus luteum
    • corpora lutea is absent in 6 week old and 4 month old females, however, pre-antral, antral and Graffian follicles appear normal   (MGI Ref ID J:134371)
  • small pituitary gland
    • proportion of pituitary gland area to whole brain area is reduced as compared to wildtype at 4 weeks, however, size difference disappears by adulthood   (MGI Ref ID J:134371)
  • growth/size phenotype
  • disproportionate dwarf   (MGI Ref ID J:134371)
  • increased lean body mass
    • significant increase in percentage of lean mass at 5-6 months as compared to wildtype   (MGI Ref ID J:134371)
  • slow postnatal weight gain
    • after weaning weight gain is slower than wildtype   (MGI Ref ID J:134371)
    • homozygotes do not exhibit juvenile growth spurt   (MGI Ref ID J:134371)
  • adipose tissue phenotype
  • decreased percent body fat
    • significant decrease in percentage of body fat at 5-6 months as compared to wildtype   (MGI Ref ID J:134371)
  • craniofacial phenotype
  • short snout
    • snub nose is visible by four months of age   (MGI Ref ID J:134371)
  • homeostasis/metabolism phenotype
  • decreased blood urea nitrogen level   (MGI Ref ID J:134371)
  • decreased circulating estradiol level
    • following injection of exogenous gonadotropin in 12-14 week old mice, estradiol levels are lower than adult wildtype and similar to prepubertal wildtype   (MGI Ref ID J:134371)
  • decreased circulating progesterone level
    • following injection of exogenous gonadotropin in 12-14 week old mice, progesterone levels are lower than adult wildtype and similar to prepubertal wildtype   (MGI Ref ID J:134371)
  • decreased circulating testosterone level
    • following injection of exogenous gonadotropin in 12-14 week old mice, testosterone levels are lower than adult wildtype and similar to prepubertal wildtype   (MGI Ref ID J:134371)
  • increased circulating glucose level   (MGI Ref ID J:134371)
  • vision/eye phenotype
  • exophthalmos
    • protuberant eyes are observed by four months of age   (MGI Ref ID J:134371)
  • skeleton phenotype
  • decreased bone mineral content
    • bone mineral content is reduced in comparison to wildtype, however density is not reduced   (MGI Ref ID J:134371)
  • reproductive system phenotype
  • abnormal spermatid morphology
    • number of spermatids is reduced in 4 month old mice, but not in 6 week old mice   (MGI Ref ID J:134371)
  • abnormal vagina opening
    • following injection of exogenous gonadotropin in 12-14 week old mice, vaginal opening is observed in 100% of prepubertal wildtype and 80% of adult homozygotes, however, the condition is pre-existing in wildtype 12-14 week old mice   (MGI Ref ID J:134371)
  • absent corpus luteum
    • corpora lutea is absent in 6 week old and 4 month old females, however, pre-antral, antral and Graffian follicles appear normal   (MGI Ref ID J:134371)
  • anovulation
    • females are anovulatory   (MGI Ref ID J:134371)
    • following injection of PMSG and hCG at 6 weeks follicular growth to the Graffian stage is induced, but, full luteinization of thecal cells does not occur   (MGI Ref ID J:134371)
  • female infertility
    • female homozygote matings to wildtype fail to produce offspring   (MGI Ref ID J:134371)
  • male germ cell apoptosis
    • atrophy is observed in spermatogonia, Leydig and Serotoli cells at 4 months   (MGI Ref ID J:134371)
  • reduced male fertility
    • occasionally homozygote males crossed to heterozygote or wildtype females produce offspring   (MGI Ref ID J:134371)
  • nervous system phenotype
  • small pituitary gland
    • proportion of pituitary gland area to whole brain area is reduced as compared to wildtype at 4 weeks, however, size difference disappears by adulthood   (MGI Ref ID J:134371)
  • cellular phenotype
  • male germ cell apoptosis
    • atrophy is observed in spermatogonia, Leydig and Serotoli cells at 4 months   (MGI Ref ID J:134371)
View Research Applications

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

Developmental Biology Research
Craniofacial and Palate Defects
Growth Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Hypothalamus/Pituitary Defects

Reproductive Biology Research
Developmental Defects Affecting Gonads
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ddr2slie
Allele Name smallie
Allele Type Spontaneous
Strain of OriginBKSChpLt.Cg-Tg(Ins2-Cpe)1Lt Cpe/LtJng
Gene Symbol and Name Ddr2, discoidin domain receptor family, member 2
Chromosome 1
Gene Common Name(s) AW495251; MIG20a; NTRKR3; Ntrkr3; TKT; TYRO10; expressed sequence AW495251; neurotrophic tyrosine kinase, receptor related 3;
Molecular Note The mutation is a deletion of approximately 150kb encompassing most of the Ddr2 gene, of which genomic PCR analysis failed to amplify exons 1-17; exon 18 of this gene and the final exon of the proximal gene, Hsd17b7, both were amplified. [MGI Ref ID J:134371]

Genotyping

Genotyping Information

Genotyping Protocols

Ddr2slie/JngJ, QPCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kano K; Marin de Evsikova C; Young J; Wnek C; Maddatu TP; Nishina PM; Naggert JK. 2008. A novel dwarfism with gonadal dysfunction due to loss-of-function allele of the collagen receptor gene, Ddr2, in the mouse. Mol Endocrinol 22(8):1866-80. [PubMed: 18483174]  [MGI Ref ID J:134371]

Additional References

Ddr2slie related

Kano K; Kitamura A; Matsuwaki T; Morimatsu M; Naito K. 2010. Discoidin domain receptor 2 (DDR2) is required for maintenance of spermatogenesis in male mice. Mol Reprod Dev 77(1):29-37. [PubMed: 19681157]  [MGI Ref ID J:157045]

Matsumura H; Kano K; de Evsikova CM; Young JA; Nishina PM; Naggert JK; Naito K. 2009. Transcriptome analysis reveals an unexpected role of a collagen tyrosine kinase receptor gene, Ddr2, as a regulator of ovarian function. Physiol Genomics 39(2):120-9. [PubMed: 19671659]  [MGI Ref ID J:155774]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as heterozygotes. Homozygotes are infertile.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   11-SEP-08
Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing
Order this mouse

Live Mice

Price (US dollars $)GenderGenotypes Provided
Individual Mouse $261.00Female or MaleHeterozygous for Ddr2slie
$320.00Female or MaleHomozygous for Ddr2slie
Pairs /Price (US dollars $)Pair Genotype
$522.00Heterozygous for Ddr2slie x Heterozygous for Ddr2slie

Standard Supply

Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.

Pricing for International shipping destinations View USA Canada and Mexico Pricing
Order this mouse

Live Mice

Price (US dollars $)GenderGenotypes Provided
Individual Mouse $339.30Female or MaleHeterozygous for Ddr2slie
$416.00Female or MaleHomozygous for Ddr2slie
Pairs /Price (US dollars $)Pair Genotype
$678.60Heterozygous for Ddr2slie x Heterozygous for Ddr2slie

Standard Supply

Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.

General Supply Notes

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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