Description

Strain Information

Type Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x Heterozygote         (Female x Male)   11-SEP-08 Species laboratory mouse H2 Haplotype d Generation F?+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 Cpe^fat/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 Cpe^fat 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

Ddr2^slie/Ddr2^slie

        BKSChpLt.Cg-Tg(Ins2-Cpe)1Lt Cpe^fat/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 Origin		BKSChpLt.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

Ddr2^slie/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

Ddr2^slie 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 & Husbandry	When maintaining a live colony, these mice are bred as heterozygotes. Homozygotes are infertile.
Mating System	Heterozygote x Heterozygote         (Female x Male)   11-SEP-08
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Mouse Mutant Resource collection.

Control Information

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

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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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