Description

Strain Information

Former Names 129/Sv-L1Camtm1Sor    (Changed: 15-DEC-04 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N?+6 (09-NOV-01)   Donating Investigator Philippe Soriano,   Fred Hutchinson Cancer Research Center

Description
The L1 gene is localized to the X chromosome. As a result, hemizygous males are affected and the mutation has to be propagated through females. Male mice hemizygous for the L1cam^tm1Sor targeted mutation have defects in the guidance of axons of the corticospinal tract. A substantial proportion of axons do not take their normal crossed course to the dorsal column at the pyramidal decussation. There is also a varying, but reduced number of corticospinal axons in the dorsal columns of the spinal cord.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying   L1cam^tm1Sor allele

003120

B6;129S7-L1camtm1Sor/J

View Strains carrying   L1cam^tm1Sor     (1 strain)

Additional Web Information

New 129 Nomenclature Bulletin

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

L1cam^tm1Sor/Y

        either: 129S7/SvEvBrd-L1cam^tm1Sor or (129S7/SvEvBrd * C57BL/6J)F1

• lethality-prenatal/perinatal
• prenatal lethality (MGI Ref ID J:45013)
  • males are born at ~40% of expected frequency (84/211 total males)
• life span-post-weaning/aging
• *normal* life span-post-weaning/aging (MGI Ref ID J:45013)
  • males survive >18 months
• growth/size phenotype
• decreased body size (MGI Ref ID J:45013)
  • initially males are ~60% size of wild-type littermates
• postnatal slow weight gain (MGI Ref ID J:45013)
  • by adulthood, males attain ~80% the size of wild-type littermates
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:45013)
  • the optic chiasm, corpus callosum, and spinal commissural projection in mutants show normal axonal pathfinding and crossing projections, in contrast to the pyramidal decussation
• abnormal axon guidance (MGI Ref ID J:45013)
  • in P3-P5 animals, very few corticospinal axons grow to the contralateral dorsal columns at the pyramidal decussation; many axons instead turn ventrally at midline and enter the contralateral pyramid
  • in one animal, aberrant axons turn rostrally in contralateral pyramid and project back towards midbrain; in other animals, axons can't be traced beyond decussation
  • no axons are apparent caudal to the decussation, either ventrally or dorsally
• abnormal corticospinal tract (MGI Ref ID J:45013)
  • in adult males examined, corticospinal axons project normally to the medulla, but at the level of the decussation, a substantial portion of axons fail to cross the midline and instead pass ipsilaterally into the dorsal columns
  • no axon labeling is detected more caudally than the cervical spinal cord in male mutants
• behavior/neurological phenotype
• abnormal motor capabilities/coordination/movement (MGI Ref ID J:45013)
• hindlimb paralysis (MGI Ref ID J:45013)
  • dragging of hindlimbs is observed in some mice >12 months of age
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:45013)
  • although males are sterile, testis contain germ cells
• male infertility (MGI Ref ID J:45013)
  • some individuals are able to breed but most are effectively sterile
• vision/eye phenotype
• enophthalmos (MGI Ref ID J:45013)
  • adult mutants have sunken eyes
• excessive tearing (MGI Ref ID J:45013)
  • adult mutants have lacrimous eyes
• skin/coat/nails phenotype
• abnormal coat color (MGI Ref ID J:45013)
  • with age, mice on congenic 129/Sv agouti background develop patches of black fur on their backs
• long toenails (MGI Ref ID J:45013)
  • mice have abnormally long hind-paw toenails (4-5 mm) on congenic 129/Sv background
• pigmentation phenotype
• abnormal coat color (MGI Ref ID J:45013)
  • with age, mice on congenic 129/Sv agouti background develop patches of black fur on their backs

L1cam^tm1Sor/Y

        involves: 129S7/SvEvBrd

• growth/size phenotype
• decreased body weight (MGI Ref ID J:47995)
  • mutants show reduced body weights
• nervous system phenotype
• abnormal axon outgrowth (MGI Ref ID J:47995)
  • cultured neurons grown on L1-Fc chimera (molecule of Fc region of human IgG and entire extracellular domain of human L1) show impaired ability to extend neurites compared to wild-type neurons; fewer neurons show outgrowth and extend shorter neurites compared to wild-type neurons
• abnormal brain morphology (MGI Ref ID J:47995)
  • total brain volume is significantly reduced compared to controls
• abnormal cerebellum morphology (MGI Ref ID J:47995)
  • cerebellar volume is significantly reduced compared to controls
  • ratio between surface of cerebellum and surface of total brain (in midsagittal sections) is reduced compared to wild-type
• vermis hypoplasia (MGI Ref ID J:47995)
  • average surface area of vermis is reduced compared to controls; ratio of surface area of vermis to cerebral cortex surface area is smaller
  • hypoplasia is most prominent in lobule 6; one or two of the three sublobule of lobule 6 are underdeveloped or missing in mutants
• abnormal cerebral aqueduct (MGI Ref ID J:47995)
  • shape is different in mutants; distal part connecting ampulla of aqueduct to fourth ventricle is longer in mutants
• abnormal fourth ventricle morphology (MGI Ref ID J:47995)
  • volume of fourth ventricle is increased compared to controls
• enlarged fourth ventricle (MGI Ref ID J:47995)
  • volume of fourth ventricle is increased compared to controls
• dilated lateral ventricles (MGI Ref ID J:47995)
  • significant dilation of lateral ventricles is observed
• behavior/neurological phenotype
• abnormal social/conspecific interaction (MGI Ref ID J:47995)
  • when a cage containing 2 female mice is placed in center of open field test cage, mutants do not adapt exploration pattern to this external stimulus; mutants still display circling of cage periphery while wild-type spend 45% of their exploratory behavior within 10 cm of the cage
• abnormal spatial learning (MGI Ref ID J:47995)
  • mutants show impaired spatial learning in Morris water-maze paradigm in probe trials where platform is removed; mutants spend significantly less time in target quadrant and majority of time is localized to periphery
• hypoactivity (MGI Ref ID J:47995)
  • mutants show ~50% of total cage activity that is displayed by wild-type controls
• impaired coordination (MGI Ref ID J:47995)
  • in rotarod trials, mutants display difficulties in maintaining balance, and fall on at least one attempt, compared to wild-type controls
• increased thigmotaxis (MGI Ref ID J:47995)
  • in open field test, most mutants spend less time exploring, instead running in circles around perimeter of cage

View Research Applications

Research Applications

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

Developmental Biology Research
Internal/Organ Defects (brain)
Neurodevelopmental Defects
Perinatal Lethality

Neurobiology Research
Ataxia (Movement) Defects
Cortical Defects
Neurodevelopmental Defects

Research Tools
Neurobiology Research

L1cam^tm1Sor related

Neurobiology Research
Neural Tube Defects
Neurotrophic Factor Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		L1camtm1Sor
Allele Name		targeted mutation 1, Philippe Soriano
Allele Type		Targeted (knock-out)
Common Name(s)		L1-;
Mutation Made By		Philippe Soriano,   Fred Hutchinson Cancer Research Center
Strain of Origin		129S7/SvEvBrd-Hprt1<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt1<+>
Gene Symbol and Name		L1cam, L1 cell adhesion molecule
Chromosome		X
Gene Common Name(s)		CAML1; CD171; HSAS; HSAS1; Hyd; L1; L1-NCAM; MASA; MIC5; N-CAML1; NCAM-L1; NCAML1; S10; SPG1;
Molecular Note		A neomycin resistance cassette replaced the exons encoding the sixth immunoglobulin-like domain of the protein. Immunoblots of lysates of adult brains from homozygous mutant mice showed an absence of normal protein. [MGI Ref ID J:45013]

Genotyping

Genotyping Information

Genotyping Protocols

L1cam^tm1Sor, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Cohen NR; Taylor JS; Scott LB; Guillery RW; Soriano P; Furley AJ. 1998. Errors in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1. Curr Biol 8(1):26-33. [PubMed: 9427628]  [MGI Ref ID J:45013]

Additional References

L1cam^tm1Sor related

Bliss T; Errington M; Fransen E; Godfraind J; Kauer JA; Kooy RF; Maness PF; Furley AJ. 2000. Long-term potentiation in mice lacking the neural cell adhesion molecule L1. Curr Biol 10(24):1607-10. [PubMed: 11137015]  [MGI Ref ID J:67186]

Demyanenko GP; Maness PF. 2003. The L1 cell adhesion molecule is essential for topographic mapping of retinal axons. J Neurosci 23(2):530-8. [PubMed: 12533613]  [MGI Ref ID J:81739]

Demyanenko GP; Shibata Y; Maness PF. 2001. Altered distribution of dopaminergic neurons in the brain of L1 null mice. Brain Res Dev Brain Res 126(1):21-30. [PubMed: 11172883]  [MGI Ref ID J:67529]

Demyanenko GP; Tsai AY; Maness PF. 1999. Abnormalities in neuronal process extension, hippocampal development, and the ventricular system of L1 knockout mice. J Neurosci 19(12):4907-20. [PubMed: 10366625]  [MGI Ref ID J:55494]

Fransen E; D'Hooge R; Van Camp G; Verhoye M; Sijbers J; Reyniers E; Soriano P; Kamiguchi H; Willemsen R; Koekkoek SK; De Zeeuw CI; De Deyn PP; Van der Linden A; Lemmon V; Kooy RF; Willems PJ. 1998. L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns. Hum Mol Genet 7(6):999-1009. [PubMed: 9580664]  [MGI Ref ID J:47995]

Haney CA; Sahenk Z; Li C; Lemmon VP; Roder J; Trapp BD. 1999. Heterophilic binding of L1 on unmyelinated sensory axons mediates Schwann cell adhesion and is required for axonal survival. J Cell Biol 146(5):1173-84. [PubMed: 10477768]  [MGI Ref ID J:57603]

Jakeman LB; Chen Y; Lucin KM; McTigue DM. 2006. Mice lacking L1 cell adhesion molecule have deficits in locomotion and exhibit enhanced corticospinal tract sprouting following mild contusion injury to the spinal cord. Eur J Neurosci 23(8):1997-2011. [PubMed: 16630048]  [MGI Ref ID J:108065]

Law CO; Kirby RJ; Aghamohammadzadeh S; Furley AJ. 2008. The neural adhesion molecule TAG-1 modulates responses of sensory axons to diffusible guidance signals. Development 135(14):2361-71. [PubMed: 18550718]  [MGI Ref ID J:137627]

Molnar Z; Higashi S; Lopez-Bendito G. 2003. Choreography of early thalamocortical development. Cereb Cortex 13(6):661-9. [PubMed: 12764042]  [MGI Ref ID J:102089]

Runyan SA; Roy RR; Zhong H; Phelps PE. 2007. L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation. Neuroscience 150(4):959-69. [PubMed: 18022323]  [MGI Ref ID J:130762]

Sakurai T; Lustig M; Babiarz J; Furley AJ; Tait S; Brophy PJ; Brown SA; Brown LY; Mason CA; Grumet M. 2001. Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development. J Cell Biol 154(6):1259-73. [PubMed: 11564762]  [MGI Ref ID J:71828]

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

 

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

Estimated Available for Sale Date: 15-OCT-04

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 Cryopreservation Repository
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
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.

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