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| These Klk4-null/lacZ knock-in (Klk4- or Klk4lacZ) mice harbor a nuclear-localized β-galactosidase "knock-in" mutation that also abolishes endogenous Klk4 (kallikrein related-peptidase 4 [prostase, enamel matrix, prostate]) gene function. These mice may be useful for studying the molecular mechanisms of enamel protein cleavage necessary for proper dental enamel formation/biomineralization/crystallization during tooth development. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
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 Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Jan CC Hu, University of Michigan Description
Mice homozygous for the Klk4-null/lacZ knock-in allele (Klk4- or Klk4lacZ) are viable and fertile, with a nuclear-localized β-galactosidase (NLS lacZ) translation initiation site and coding region replacing the Klk4 translation initiation site and coding region. This abolishes endogenous gene function. Under control of the upstream promoter/enhancer elements, lacZ expression is directed to ameloblasts (the enamel-forming cells in developing teeth) during the transition and maturation stages of dental enamel formation. Klk4-deficiency results in improper dental enamel matrix biomineralization, altered gross tooth morphology, and premature tooth decay. Homozygous mice exhibit malformed enamel that is rapidly abraded after weaning (even when fed moistened chow) and a tendency for all teeth to fracture at points of contact. Heterozygous mice appear indistinguishable from wildtype mice. These Klk4lacZ mice may be useful for studying the molecular mechanisms of enamel protein cleavage necessary for proper dental enamel formation/biomineralization/crystallization during tooth development.NLS lacZ activity may be readily distinguished from native mouse lacZ activity by its nuclear localization and high pH optima: mouse β-galactosidase is a lysosomal enzyme that is only marginally active at pH 7.5, whereas bacterial β-galactosidase can be strongly detected above pH 8 (Weiss et al, 1999 Histochem J 31:231).
Development
A targeting vector was designed to insert a nuclear-localized β-galactosidase (NLS lacZ) gene and loxP-flanked PGK-Neo cassette into the first coding exon (exon 2), and also delete the entire coding region (exons 2-6), of the kallikrein 4 gene. This replaces the Klk4 translation initiation site and coding region with the NLS lacZ translation initiation site and coding region. The construct was electroporated into C57BL/6-derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and male chimeras were mated to C57BL/6J females. Next, mutant mice were bred to "B6 Cre deleter" mice (coisogneic on C57BL/6) to remove the floxed neo cassette. The resulting mice harboring the Klk4-null/lacZ knock-in allele (Klk4- or Klk4lacZ) were selectively bred to remove the Cre transgene and then backcrossed to C57BL/6J mice for at least six generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (255 strains)
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Amelogenesis Imperfecta, Hypomaturation Type, Iia1; AI2A1 (KLK4)
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Klk4tm1.1Jpsi/Klk4tm1.1Jpsi
involves: Black Swiss * C57BL/6
- mortality/aging
- premature death
- craniofacial phenotype
- abnormal enamel morphology
- the erupted portion of mandibular incisors are chalky white unlike in wild-type mice (MGI Ref ID J:151626)
- the enamel of all teeth tends to fracture at point of contact with opposing dentition unlike in wild-type mice (MGI Ref ID J:151626)
- enamel strength is reduced compared to in wild-type mice (MGI Ref ID J:151626)
- enamel abrades rapidly following weaning despite a soft diet (MGI Ref ID J:151626)
- growth/size phenotype
- postnatal growth retardation
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype
- mice exhibit normal serum levels of calcium, phosphate, magnesium, alanine aminotransferase, and total protein (MGI Ref ID J:151626)
This mouse can be used to support research in many areas including:
Developmental Biology Research
Skeletal Defects
Internal/Organ Research
Other
Research Tools
lacZ Expression
Genetics Research
Tissue/Cell Markers
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Klk4tm1.1Jpsi | ||
|---|---|---|---|
| Allele Name | targeted allele 1.1, James P Simmer | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Klk4lacZ; | ||
| Mutation Made By | Jan CC Hu, University of Michigan | ||
| Strain of Origin | B6.Cg-Thy1 | ||
| Site of Expression | lacZ expression is directed to ameloblasts (the enamel-forming cells in developing teeth) during the transition and maturation stages of dental enamel formation. | ||
| Gene Symbol and Name | Klk4, kallikrein related-peptidase 4 (prostase, enamel matrix, prostate) | ||
| Chromosome | 7 | ||
| Gene Common Name(s) | AI2A1; ARM1; EMSP; EMSP1; ESMP1; KLK-L1; PRSS17; PSTS; Prss17; kallikrein; protease, serine 17 (enamel matrix, prostate); | ||
| Molecular Note | The genomic sequence spanning the initiation codon in exon 2 through exon 6 was replaced with an NLS-lacZ and floxed neo cassette. The neo cassette was subsequently removed by germ line, cre mediated recombination. This allele lacks the entire coding region. [MGI Ref ID J:151626] | ||
References
References provided by MGI
Selected Reference(s)
Simmer JP; Hu Y; Lertlam R; Yamakoshi Y; Hu JC. 2009. Hypomaturation enamel defects in Klk4 knockout/LacZ knockin mice. J Biol Chem 284(28):19110-21. [PubMed: 19578120] [MGI Ref ID J:151626]
Additional References
Klk4tm1.1Jpsi relatedSmith CE; Richardson AS; Hu Y; Bartlett JD; Hu JC; Simmer JP. 2011. Effect of Kallikrein 4 Loss on Enamel Mineralization: COMPARISON WITH MICE LACKING MATRIX METALLOPROTEINASE 20. J Biol Chem 286(20):18149-60. [PubMed: 21454549] [MGI Ref ID J:172681]
Health & husbandry
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.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). Homozygous mice have "soft teeth" and benefit from being fed moistened chow.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| 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.Ordering Information
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