|These targeted mutant mice have increased anxiety-related behavior and impaired contextual fear memory. Homozygous targeted mutant mice have enhanced performance in a spatial learning task, however long-term memory retention is impaired. This strain may be useful in studies of cognitive processes, a feature that may be relevant to human autism spectrum disorders.|
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N?pN1
Donating Investigator Morgan Sheng, Massachusetts Institute of Technology
Homozygous targeted mutant mice show altered postsynaptic density (PSD) protein composition (depletion of Shank-associated proteins guanylate kinase-associated protein (GKAP) and homer homolog 1 (HOMER)), reduced size of dendritic spines, smaller and thinner PSD's, and weaker basal synaptic transmission in the brain. Synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD), and late-phase LTP (L-LTP) is normal. Behaviorally, they have increased anxiety-related behavior and impaired contextual fear memory. Homozygous targeted mutant mice have enhanced performance in a spatial learning task, however long-term memory retention is impaired. This strain may be useful in studies of cognitive processes, a feature that may be relevant to human autism spectrum disorders.
A targeting vector was designed to replace exons 14 and 15, encoding almost the entire PDZ domain, with a PGK-neomycin drug resistance cassette. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Heterozygous offspring were backcrossed to C57BL/6 at least 13 times by the donating laboratory.
Strains carrying Shank1tm1Shng allele
008109 129S4/SvJae-Shank1tm1Shng/JView Strains carrying Shank1tm1Shng (1 strain)
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.
Shank1tm1Shng/Shank1tm1Shnginvolves: 129S4/SvJae * C57BL/6
- nervous system phenotype
- *normal* nervous system phenotype
- abnormal CNS synapse formation
- abnormal CNS synaptic transmission
- basal synaptic transmission at the Schaffer collateral/commissural-CA1 synapse in hippocampal slices is reduced; input-output curve is shifted downward at high stimulus intensities (MGI Ref ID J:132277)
- abnormal hippocampus pyramidal cell morphology
- behavior/neurological phenotype
- abnormal maternal nurturing
- females do not nurture their offspring; litters generally die before weaning (MGI Ref ID J:132277)
- abnormal spatial learning
- mutants learn faster and more effectively than wild-type during repetitive training in the eight-armed radial maze (MGI Ref ID J:132277)
- abnormal spatial reference memory
- in eight-armed radial maze testing paradigm, mutants show enhanced reference memory compared to wild-type; mutants show fewer reference memory errors than wild-type, even with prolonged training (MGI Ref ID J:132277)
- when tested for 're-learning' using reversal training in the radial maze paradigm, mutants show faster learning and fewer reference memory errors with repeated training (MGI Ref ID J:132277)
- abnormal long term spatial reference memory
- long-term retention of reference memory after end of training is impaired relative to wild-type (MGI Ref ID J:132277)
- when re-tested after 4 weeks, mutants regress to wild-type performance level, losing the enhancemed learning displayed in the initial testing, while wild-type performance after 28 days is similar to the original level during testing (MGI Ref ID J:132277)
- abnormal spatial working memory
- in eight-armed radial maze testing paradigm, mutants show enhanced working memory, making fewer working memory errors than wild-type animals (MGI Ref ID J:132277)
- hypoactivity (MGI Ref ID J:132277)
- impaired coordination
- mild deficit demonstrated by reduced latency to fall in accelerating rotarod test (MGI Ref ID J:132277)
- increased anxiety-related response
- mutants display increased anxiety-like behavior in open-field and light/dark exploration tests relative to wild-type (MGI Ref ID J:132277)
- reproductive system phenotype
- reduced fertility
- mice are poor breeders, rarely giving birth (MGI Ref ID J:132277)View Research Applications
|Allele Name||targeted mutation 1, Morgan Sheng|
|Allele Type||Targeted (Null/Knockout)|
|Mutation Made By||Morgan Sheng, Massachusetts Institute of Technology|
|Strain of Origin||129S4/SvJae|
|Gene Symbol and Name||Shank1, SH3/ankyrin domain gene 1|
|Gene Common Name(s)||SPANK-1; SSTRIP; Shank1a; Spank1; synamon;|
|Molecular Note||A targeting vector was designed to replace exons 14 and 15, encoding almost the entire PDZ domain, with a PGK-neomycin drug resistance cassette. The absence of protein product was confirmed by western blot analysis on forebrain membrane extracts. [MGI Ref ID J:132277]|
Hung AY; Futai K; Sala C; Valtschanoff JG; Ryu J; Woodworth MA; Kidd FL; Sung CC; Miyakawa T; Bear MF; Weinberg RJ; Sheng M. 2008. Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J Neurosci 28(7):1697-708. [PubMed: 18272690] [MGI Ref ID J:132277]
Silverman JL; Turner SM; Barkan CL; Tolu SS; Saxena R; Hung AY; Sheng M; Crawley JN. 2011. Sociability and motor functions in Shank1 mutant mice. Brain Res 1380:120-37. [PubMed: 20868654] [MGI Ref ID J:170750]
Stella SL Jr; Vila A; Hung AY; Rome ME; Huynh U; Sheng M; Kreienkamp HJ; Brecha NC. 2012. Association of shank 1A scaffolding protein with cone photoreceptor terminals in the mammalian retina. PLoS One 7(9):e43463. [PubMed: 22984429] [MGI Ref ID J:191880]
Wohr M; Roullet FI; Hung AY; Sheng M; Crawley JN. 2011. Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior. PLoS One 6(6):e20631. [PubMed: 21695253] [MGI Ref ID J:174446]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry When maintaining a live colony, heterozygotes may be bred. Homozygous females have decreased fertility and rarely give birth to litters; when produced, litters are small and pups do not survive to weaning.
|Pricing for USA, Canada and Mexico shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2140.00
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.
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 10 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 Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2782.00
Cryorecovery - Standard.
Progeny testing is not required.
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