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Genes & Alleles

Timp2;   Timp2tm1Pds;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Species laboratory mouse Donating Investigator Paul Soloway,   Cornell University

Strain Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by Northern blot analysis of lung tissue. Mutant mice are unable to proteolytically activate proMMP-2, proenzyme matrix metalloproteinase-2. Male homozygotes exhibit deficits in fear-potentiated startle respnses and both male and female mutants exhibit reduced prepulse inhibition. Homozygotes exhibit muscle weakness (due to reduced mass of extensor digitorum longus fast-twitch muscle), decreased motor function, abnormal gait and reduced hindlimb extension. The brains of homozygotes in the postnatal week are smaller in size than wildtype controls, with the size difference disappearing after postnatal day 7. Histological analysis reveals abnormal neuromuscular junctions characterized by a larger size with increased nerve branching, reduced cerebellar cortex thickness, and reduced Purkinje cell processes. Homozygotes have impaired neuronal differentiation. Female homozygotes are passive when handled, while male homozygotes are aggressive. This mutant mouse strain may be useful in studies of extracellular matrix homeostasis, synaptic plasticity in behavior, learning and memory, neuronal differentiation and development of neuromuscular junctions.

Strain Development
A targeting vector containing PGKneo cassette was used to disrupt exon 1 and 5' flanking sequence. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to generate homozygous mice. The mice were then backcrossed to C57BL/6 J for 12 generations before arriving at The Jackson Laboratory.

Mammalian Phenotype Terms assigned by genotype Timp2tm1Pds/Timp2tm1Pds         B6.129S4-Timp2tm1Pds behavior/neurological phenotype abnormal cued conditioning behavior (MGI Ref ID J:99752) null mice have a deficit in fear-potentiated startle (FPS) vs wild type; mice generate greater startle responses compared to wild type mice in presence of tone before fear conditioning (ie. P0 - first testing session) all males show an increase in FPS initially (from P0 to P1) but FPS decreases from that point in knockout and knockdown mice; in wild type and heterozygotes, amplitudes of startle responses continue to increase wild type and heterozygous males acquire conditioned fear over the course of the test, but null and knockdown mice do not females do not show any proportional increases in FPS nervous system phenotype abnormal prepulse inhibition (MGI Ref ID J:99752) Timp2-null mice have significantly reduced prepulse inhibition (PPI) The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. Timp2tm1Pds/Timp2tm1Pds         involves: 129S4/SvJae * C57BL/6 hematopoietic system phenotype increased neutrophil cell number (MGI Ref ID J:112941) at day 7 after treatment, BAL neutrophil percentage and concentration are 3- and 10-fold higher in Timp1-null mice compared to Timp2-null animals; values for Timp2-null mice are similar to wild type immune system phenotype increased neutrophil cell number (MGI Ref ID J:112941) at day 7 after treatment, BAL neutrophil percentage and concentration are 3- and 10-fold higher in Timp1-null mice compared to Timp2-null animals; values for Timp2-null mice are similar to wild type homeostasis/metabolism phenotype abnormal enzyme/coenzyme activity (MGI Ref ID J:64001) activation of proMMP-2 in vivo is dramatically altered with Timp2 deficiency

Gene & Allele Details

Allele Symbol		Timp2tm1Pds
Allele Name		targeted mutation 1, Paul D Soloway
Common Name(s)		TIMP-2KO; TIMP2KO; Timp2-;
Mutation Made By		Paul Soloway,   Cornell University
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Timp2, tissue inhibitor of metalloproteinase 2
Chromosome		11
Gene Common Name(s)		CSC-21K; D11Bwg1104e; DNA segment, Chr 11, Brigham & Women's Genetics 1104 expressed; MGC105282; TIMP-2; Timp-2;
Molecular Note		Replacement of the first coding exon with a neomycin cassette. [MGI Ref ID J:64001]

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.

Additional Web Information

Congenic Nomenclature

Research Applications

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

Cell Biology Research
Defects in Extracellular Matrix Molecules

Developmental Biology Research
Defects in Extracellular Matrix Molecules
Neurodevelopmental Defects

Neurobiology Research
Ataxia (Movement) Defects
Behavioral and Learning Defects
Cerebellar Defects (Purkinje cell defect)
Neurodevelopmental Defects
Neuromuscular Defects

References

Selected Reference(s)

Wang Z; Juttermann R; Soloway PD. 2000. TIMP-2 is required for efficient activation of proMMP-2 in vivo J Biol Chem 275(34):26411-5. [PubMed: 10827175]  [MGI Ref ID J:64001]

Additional References

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Price and Supply Information

Strain Name:	B6.129S4-Timp2tm1Pds/J
Stock Number:	008120

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

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Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection.
Licensing	See General Terms and Conditions below

General Terms and Conditions

View JAX^® Mice & Services Conditions of Use.

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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