Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129X1 x 129S1 via R1 (+Kitl-SlJ) ES cell line Generation N?+3   Donating Investigator Joseph Marszalek,   UCSD-HHMI

Description
Ciliary formation appears to be crucial in developing left-right asymmetry in early mouse embryonic development. One of the necessary cilia components is the Kif3a gene product. Homozygous Kif3a knockout mice die at 10 days postcoitum, exhibit randomized establishment of left-right asymmetry and display numerous structural abnormalities. Cardiac looping is randomized, often retarded. Growth is severely retarded with caudal truncation. A neural tube closure defect is also apparent. Scanning electron microscopy indicates the absence of embryonic cilia. A small percentage of heterozygotes exhibit morphological abnormalities.

Additional Web Information

Congenic Nomenclature

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.

Kif3a^tm1Gsn/Kif3a⁺

        involves: 129S1/Sv * 129X1/SvJ

• embryogenesis phenotype
• abnormal embryo turning (MGI Ref ID J:54575)
  • at E9.5, a subset (4 of 34) heterozygotes fail to undergo turning from lordotic to fetal position
• reduced embryo size (MGI Ref ID J:54575)
  • after E9.0, a subset (4 of 34) heterozygotes appear smaller than all wild-type embryos and most heterozygous (30/34) littermates
• cardiovascular system phenotype
• abnormal looping morphogenesis (MGI Ref ID J:54575)
  • at E9.5, a subset (4 of 34) heterozygotes display retarded but normal cardiac looping along with pericardial edema
• pericardial edema (MGI Ref ID J:54575)
  • at E9.5, a subset (4 of 34) heterozygotes display pericardial edema
• growth/size phenotype
• reduced embryo size (MGI Ref ID J:54575)
  • after E9.0, a subset (4 of 34) heterozygotes appear smaller than all wild-type embryos and most heterozygous (30/34) littermates
• homeostasis/metabolism phenotype
• pericardial edema (MGI Ref ID J:54575)
  • at E9.5, a subset (4 of 34) heterozygotes display pericardial edema

Kif3a^tm1Gsn/Kif3a^tm1Gsn

        involves: 129S1/Sv * 129X1/SvJ

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:54575)
  • homozygotes die at E10
• embryogenesis phenotype
• abnormal Henson's node morphology (MGI Ref ID J:54575)
  • at E7.0-E7.5, the mutant embryonic node is normally positioned; however, the nodal plate appears flatter than normal, and overgrowth of surrounding endodermal cells is often observed
  • no other obvious morphological defects are noted prior to E9.0
• absent embryonic cilia (MGI Ref ID J:54575)
  • at E7.0-E7.5, homozygotes consistently lack cilia on all cells of the embryonic node
• abnormal embryo turning (MGI Ref ID J:54575)
  • at E9.5, all homozygotes fail to undergo turning from lordotic to fetal position
• abnormal left-right axis patterning (MGI Ref ID J:54575)
  • at E9.5, homozygotes display randomized establishment of L-R asymmetry
• branchial arch hypoplasia (MGI Ref ID J:54575)
  • at E9.5, all homozygotes exhibit reduced branchial arches
• caudal body truncation (MGI Ref ID J:54575)
  • at E9.5, all homozygotes are caudally truncated
• reduced embryo size (MGI Ref ID J:54575)
  • after E9.0, all homozygous mutant embryos appear smaller than wild-type embryos
• cardiovascular system phenotype
• abnormal direction of looping morphogenesis (MGI Ref ID J:54575)
  • at E9.5, homozygotes exhibit randomized heart looping: 4 of 13 homozygotes show reversed cardiac looping while 3 of 13 display retarded looping accompanied by pericardial edema; the remaining (6 of 13) homozygotes show normal cardiac looping
• pericardial edema (MGI Ref ID J:54575)
  • at E9.5, many homozygotes show a globular pericardium with edema
• growth/size phenotype
• reduced embryo size (MGI Ref ID J:54575)
  • after E9.0, all homozygous mutant embryos appear smaller than wild-type embryos
• situs inversus (MGI Ref ID J:54575)
  • at E9.5, 4 of 13 homozygotes show reversed cardiac looping
• limbs/digits/tail phenotype
• abnormal limb development (MGI Ref ID J:54575)
  • at E9.5, all homozygotes exhibit reduced or absent limb primordia
• nervous system phenotype
• abnormal neural tube closure (MGI Ref ID J:54575)
  • at E9.5, all homozygotes display defects in neural tube closure
• craniofacial phenotype
• branchial arch hypoplasia (MGI Ref ID J:54575)
  • at E9.5, all homozygotes exhibit reduced branchial arches
• homeostasis/metabolism phenotype
• pericardial edema (MGI Ref ID J:54575)
  • at E9.5, many homozygotes show a globular pericardium with edema

View Research Applications

Research Applications

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

Kif3a^tm1Gsn related

Cardiovascular Research
Heart Abnormalities

Cell Biology Research
Cell Motility Defects

Developmental Biology Research
Cell Motility Defects (situs inversus)
Growth Defects
Internal/Organ Defects
Neural Tube Defects
Postnatal Mortality (Homozygous)
Skeletal Defects

Internal/Organ Research
Heart Abnormalities

Neurobiology Research
Neural Tube Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Kif3atm1Gsn
Allele Name		targeted mutation 1, Lawrence SB Goldstein
Allele Type		Targeted (knock-out)
Common Name(s)		KIF3A-; Kif3an; Kif3atm1Maz;
Mutation Made By		Joseph Marszalek,   UCSD-HHMI
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Kif3a, kinesin family member 3A
Chromosome		11
Gene Common Name(s)		AF180004; AF180009; AW124694; DNA sequence AF180004; DNA sequence AF180009; Kif3; Kifl; Kns3; N-4 kinesin; expressed sequence AW124694; kinesin family member 3; kinesin family-like; kinesin-II subunit;
Molecular Note		Exon 2 was deleted by cre recombinase removal of a targeting vector containing the exon flanked by loxP sites. The resulting transcript was translated out of reading frame, generating a 62 amino acid nonsense protein. Northern and Western blots of heterozygous mutants showed that no fragments or aberrant products were made from the mutant gene. Western blots of homozygous mutants showed an absence of the targeted protein. [MGI Ref ID J:54575]

Genotyping

Genotyping Information

Genotyping Protocols

Kif3a^tm1Gsn, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Marszalek JR; Ruiz-Lozano P; Roberts E; Chien KR; Goldstein LS. 1999. Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II. Proc Natl Acad Sci U S A 96(9):5043-8. [PubMed: 10220415]  [MGI Ref ID J:54575]

Additional References

Kif3a^tm1Gsn related

Cho A; Ko HW; Eggenschwiler JT. 2008. FKBP8 cell-autonomously controls neural tube patterning through a Gli2- and Kif3a-dependent mechanism. Dev Biol 321(1):27-39. [PubMed: 18590716]  [MGI Ref ID J:138713]

Gresh L; Fischer E; Reimann A; Tanguy M; Garbay S; Shao X; Hiesberger T; Fiette L; Igarashi P; Yaniv M; Pontoglio M. 2004. A transcriptional network in polycystic kidney disease. EMBO J 23(7):1657-68. [PubMed: 15029248]  [MGI Ref ID J:131271]

Haycraft CJ; Zhang Q; Song B; Jackson WS; Detloff PJ; Serra R; Yoder BK. 2007. Intraflagellar transport is essential for endochondral bone formation. Development 134(2):307-16. [PubMed: 17166921]  [MGI Ref ID J:117033]

Huangfu D; Anderson KV. 2005. Cilia and Hedgehog responsiveness in the mouse. Proc Natl Acad Sci U S A 102(32):11325-30. [PubMed: 16061793]  [MGI Ref ID J:100466]

Huangfu D; Liu A; Rakeman AS; Murcia NS; Niswander L; Anderson KV. 2003. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426(6962):83-7. [PubMed: 14603322]  [MGI Ref ID J:86437]

Raya A; Kawakami Y; Rodriguez-Esteban C; Buscher D; Koth CM; Itoh T; Morita M; Raya RM; Dubova I; Bessa JG; de la Pompa JL; Belmonte JC. 2003. Notch activity induces Nodal expression and mediates the establishment of left-right asymmetry in vertebrate embryos. Genes Dev 17(10):1213-8. [PubMed: 12730123]  [MGI Ref ID J:83387]

Spassky N; Han YG; Aguilar A; Strehl L; Besse L; Laclef C; Ros MR; Garcia-Verdugo JM; Alvarez-Buylla A. 2008. Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool. Dev Biol 317(1):246-59. [PubMed: 18353302]  [MGI Ref ID J:136079]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

General Terms and Conditions

See Terms 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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Contact Information
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.