Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N11+F1 (09-FEB-09)   Donating Investigator Kuo-Ping Huang,   NICHD, NIH

Description
Homozygous neurogranin-deficient (Ng-/-) mice are viable and fertile (although the donating investigator reports that homozygous females do not nurse their pups as well as wildtype or heterozygous mothers). Homozygotes have no mRNA or protein from the targeted gene observed in brain tissues. Expression of lacZ is observed in a manner consistent with the endogenous gene. Ng-/- mice exhibit impaired spatial learning, altered hippocampal short- and long-term plasticity (including long-term potentiation induction), and decreased activated CaMKII. Heterozygotes show similar, yet milder, effects. These neurogranin- (Ng or RC3)-mutant mice may be useful for neurological studies involving memory and learning, neuronal signaling pathways (including calmodulin, alpha-CaMKII, protein kinase A, protein kinase C, MAPK, and CREB), attention deficit-hyperactivity disorder (ADHD), and schizophrenia.

Development
A targeting vector was designed to replace the first five amino acids in exon 1 and the adjoining 98 bp of the first intron of the targeted gene with the lacZ and neomycin resistance genes. This construct was electroporated into 129/Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric males were bred with C57BL/6 females to generate mutant mice. Next, mutant mice were backcrossed to C57BL/6J for at least 10 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Fluorescent Proteins/lacZ Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Nrgn^tm1Kph/Nrgn⁺

        involves: 129/Sv * C57BL/6

• behavior/neurological phenotype
• abnormal contextual conditioning (MGI Ref ID J:65166)
  • mice exhibit impaired long term memory in contextual fear conditioning test
• abnormal spatial learning (MGI Ref ID J:65166)
  • spatial learning impairment in Morris water maze test although not as severely as homozygote

Nrgn^tm1Kph/Nrgn^tm1Kph

        involves: 129/Sv * C57BL/6

• nervous system phenotype
• abnormal long term potentiation (MGI Ref ID J:65166)
  • mice exhibit impaired long term potentiation (LTP) in the CA1 region and altered induction of LTP
• impaired synaptic plasticity (MGI Ref ID J:65166)
  • mice exhibit impaired short term plasticity and altered induction
• behavior/neurological phenotype
• abnormal spatial learning (MGI Ref ID J:65166)
  • spatial learning impairment in Morris water maze test

Genes & Alleles

Gene & Allele Information

Allele Symbol		Nrgntm1Kph
Allele Name		targeted mutation 1, Kuo-Ping Huang
Allele Type		Targeted (Reporter)
Common Name(s)		Ng-;
Mutation Made By		Kuo-Ping Huang,   NICHD, NIH
Strain of Origin		129/Sv
ES Cell Line Strain		129
Site of Expression		lacZ is observed in a manner consistent with the endogenous gene
Gene Symbol and Name		Nrgn, neurogranin
Chromosome		9
Gene Common Name(s)		0710001B06Rik; AI838505; NG; NG/RC3; Pss1; R75334; RC3; RIKEN cDNA 0710001B06 gene; expressed sequence AI838505; expressed sequence R75334; hng; postsynaptic spine 1; protein kinase C substrate;
Molecular Note		Insertion of a LacZ gene in frame into the first coding exon, followed by a neomycin cassette. No NRGN immunoreactivity was detected in brain sections derived from homozygous mutant mice. X-gal staining in homozygous mutant mice corresponded with the NRGN positive staining in wild-type mice. [MGI Ref ID J:65166]

Genotyping

Genotyping Information

Genotyping Protocols

Nrgn^tm1Kph, STD PCR, vers. 1

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Pak JH; Huang FL; Li J; Balschun D; Reymann KG; Chiang C; Westphal H; Huang KP. 2000. Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: A study with knockout mice Proc Natl Acad Sci U S A 97(21):11232-7. [PubMed: 11016969]  [MGI Ref ID J:65166]

Additional References

Nrgn^tm1Kph related

Huang FL; Huang KP; Boucheron C. 2007. Long-term enrichment enhances the cognitive behavior of the aging neurogranin null mice without affecting their hippocampal LTP. Learn Mem 14(8):512-9. [PubMed: 17671107]  [MGI Ref ID J:147821]

Huang FL; Huang KP; Wu J; Boucheron C. 2006. Environmental enrichment enhances neurogranin expression and hippocampal learning and memory but fails to rescue the impairments of neurogranin null mutant mice. J Neurosci 26(23):6230-7. [PubMed: 16763030]  [MGI Ref ID J:109216]

Huang KP; Huang FL; Jager T; Li J; Reymann KG; Balschun D. 2004. Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediated signaling. J Neurosci 24(47):10660-9. [PubMed: 15564582]  [MGI Ref ID J:96809]

Wu J; Huang KP; Huang FL. 2003. Participation of NMDA-mediated phosphorylation and oxidation of neurogranin in the regulation of Ca2+- and Ca2+/calmodulin-dependent neuronal signaling in the hippocampus. J Neurochem 86(6):1524-33. [PubMed: 12950461]  [MGI Ref ID J:126729]

Wu J; Li J; Huang KP; Huang FL. 2002. Attenuation of protein kinase C and cAMP-dependent protein kinase signal transduction in the neurogranin knockout mouse. J Biol Chem 277(22):19498-505. [PubMed: 11912190]  [MGI Ref ID J:76761]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous females are bred with homozygous males. The donating investigator reports that homozygous females do not nurse their pups as well as wildtype or heterozygous mothers.
Mating System	Heterozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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Terms of Use

Terms of Use

General Terms and Conditions

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Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

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