Strain Name:

STOCK En1tm1Alj/J

Stock Number:

002656

Availability:

Repository-Cryopreserved

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation+N1
 
Donating Investigator Alexandra Joyner,   New York University Medical Center

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the En1tm1Alj targeted mutation die shortly after birth. They are missing the third and fourth cranial nerves as well as most of the colliculi and cerebellum. The brain phenotype can be less severe depending on the genetic background. There is also a disruption of the dorsal/ventral patterning of the limb paws, a disrupted sterum, and truncation of the 13th ribs. Deletion of mid-hindbrain tissue may be seen as early as embryonic day 9.5.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   En1tm1Alj allele
003343   B6.129S2-En1tm1Alj/J
View Strains carrying   En1tm1Alj     (1 strain)

Strains carrying other alleles of En1
007912   STOCK En1tm2Alj/J
007916   STOCK En1tm6(cre)Alj/J
007917   STOCK En1tm7(cre/ESR1)Alj/J
View Strains carrying other alleles of En1     (3 strains)

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.

En1tm1Alj/En1tm1Alj

        involves: 129/Sv * C57BL/6J
  • limbs/digits/tail phenotype
  • abnormal apical ectodermal ridge (MGI Ref ID J:45301)
    • ectopic expression ventrally of markers for the apical ectodermal ridge
  • embryogenesis phenotype
  • abnormal apical ectodermal ridge (MGI Ref ID J:45301)
    • ectopic expression ventrally of markers for the apical ectodermal ridge

En1tm1Alj/En1tm1Alj

        either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)
  • lethality-prenatal/perinatal
  • neonatal lethality (MGI Ref ID J:19212)
    • death usually within 24 hours of birth
    • one mouse with a less severe phenotype survived to 7 days
  • embryogenesis phenotype
  • abnormal apical ectodermal ridge (MGI Ref ID J:34307)
    • thinner than in controls at E10.5
  • limbs/digits/tail phenotype
  • abnormal apical ectodermal ridge (MGI Ref ID J:34307)
    • thinner than in controls at E10.5
  • abnormal limb morphology (MGI Ref ID J:34307)
    • in limbs examined, ventral tendons of digit flexor muscles are absent or poorly developed
    • abnormal paw/hand/foot morphology (MGI Ref ID J:34307)
      • dorsal transformation of ventral structures and ventral duplication of distal structures is observed in neonatal limbs
      • paws display aspects of double dorsal paws
      • abnormal digit morphology (MGI Ref ID J:19212)
        • outward splayed digits
        • skin wrinkles on digits
        • digits flex dorsally rather than ventrally
        • ectopic digits (MGI Ref ID J:34307)
          • occasional ectopic ventral digits (digits 6, 7) are seen emanating from proximal paw pads in 10-15% of neonates
        • polydactyly (MGI Ref ID J:19212)
          • 6th postaxial digit
          • often with only one phalange
          • usually involves only one forelimb
          • one example of a preaxial supernumary digit on one paw (7 digits)
        • syndactyly (MGI Ref ID J:19212)
        • truncation of digits (MGI Ref ID J:19212)
          • mild truncation
      • abnormal foot pad morphology (MGI Ref ID J:34307)
        • circumferential nails supplant distal, ventral foot pads; proximal metatarsal pads are present but possess few is any eccrine glands
      • abnormal palmar eccrine gland morphology (MGI Ref ID J:34307)
        • ventrally restricted eccrine glands are largely absent
  • abnormal skeleton extremities morphology (MGI Ref ID J:34307)
    • ventral skeletal elements such as falciform and sesamoid cartilages are absent or incompletely formed
    • in limbs examined, ventral tendons of digit flexor muscles are absent or poorly developed (flexor digitorum profundus tendon is poorly developed, resembling extensor digitorum profundus tendon, and flexor digitorum superficialis tendon is absent
  • skeleton phenotype
  • abnormal axial skeleton morphology (MGI Ref ID J:19212)
    • decreased rib number (MGI Ref ID J:19212)
      • 13th rib pair missing or severely truncated in about 43% of animals
    • short sternum (MGI Ref ID J:19212)
      • length reduced by 25%
      • ossification centers reduced rostrally to caudally by 40-80%
      • ossification centers asymmetric and abnormally fused in the midline
      • fourth ossification center absent or rudimentary
  • abnormal skeleton extremities morphology (MGI Ref ID J:34307)
    • ventral skeletal elements such as falciform and sesamoid cartilages are absent or incompletely formed
    • in limbs examined, ventral tendons of digit flexor muscles are absent or poorly developed (flexor digitorum profundus tendon is poorly developed, resembling extensor digitorum profundus tendon, and flexor digitorum superficialis tendon is absent
  • delayed bone ossification (MGI Ref ID J:19212)
    • delayed ossification of phalanges
  • behavior/neurological phenotype
  • abnormal suckling behavior (MGI Ref ID J:19212)
    • pups fail to eat
  • aphagia (MGI Ref ID J:19212)
    • most mice fail to eat
    • only one, with a less severe phenotype actually ate
  • nervous system phenotype
  • abnormal brain morphology (MGI Ref ID J:19212)
    • abnormal brain development (MGI Ref ID J:19212)
      • abnormalities in the brain are apparent by E12.5, before primordia for the cerebellum and colliculi form
      • abnormal midbrain development (MGI Ref ID J:19212)
        • reduced in size by E9.5
        • abnormalities less obvious at E8.5
    • abnormal cerebellum morphology (MGI Ref ID J:19212)
      • variable reduction in size
      • absent cerebellum (MGI Ref ID J:19212)
        • in extreme examples, the cerebellum can be absent
    • abnormal choroid plexus morphology (MGI Ref ID J:19212)
      • fused to the truncated colliculi
    • decreased inferior colliculus size (MGI Ref ID J:19212)
      • truncated
  • abnormal cranial nerve morphology (MGI Ref ID J:19212)
    • absent oculomotor nerve (MGI Ref ID J:19212)
      • missing at E10.5 and E12.5
    • absent trochlear nerve (MGI Ref ID J:19212)
      • missing at E10.5 and E12.5
  • skin/coat/nails phenotype
  • abnormal dermal papilla (MGI Ref ID J:34307)
    • present at base of epithelial structures in ventral and dorsal dermis
  • abnormal hair follicle development (MGI Ref ID J:34307)
    • dorsally restricted follicles are seen along ventral as well as dorsal digit surfaces; ectopic ventral hairs on distal limbs
  • abnormal nail morphology (MGI Ref ID J:34307)
    • in newborn mice, nails on digits 1-4 are circumferential in contrast to dorsally-positioned nails in wild-type neonates; nail plates are found on ventral and dorsal digit surfaces
  • wrinkled skin (MGI Ref ID J:19212)
    • skin wrinkles on digits
  • endocrine/exocrine gland phenotype
  • abnormal palmar eccrine gland morphology (MGI Ref ID J:34307)
    • ventrally restricted eccrine glands are largely absent

En1tm1Alj/En1tm1Alj

        B6.129-En1tm1Alj
  • lethality-postnatal
  • postnatal lethality (MGI Ref ID J:84363)
    • born in normal numbers
    • reduced vitality and frequently die before weaning
  • growth/size phenotype
  • decreased body size (MGI Ref ID J:84363)
    • smaller than littermates within a few days of birth
  • nervous system phenotype
  • abnormal cerebellar lobule formation (MGI Ref ID J:84363)
    • fusion of cerebellar lobules IV and V
    • otherwise phenotypically normal cerebellum is seen as early as the third backcross generation to C57BL/6 and thereafter
  • decreased inferior colliculus size (MGI Ref ID J:84363)
    • mild truncation seen in the midbrain in the area of the inferior colliculi
  • limbs/digits/tail phenotype
  • abnormal paw/hand/foot morphology (MGI Ref ID J:84363)
    • fur growth on the ventral surface of the forepaws
    • abnormal digit morphology (MGI Ref ID J:84363)
      • circumferential nails on all digits
      • polydactyly (MGI Ref ID J:84363)
        • 6th postaxial digit
        • ectopic digits
      • syndactyly (MGI Ref ID J:84363)
  • skin/coat/nails phenotype
  • deformed nails (MGI Ref ID J:84363)
    • circumferential nails on all digits
View Research Applications

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

En1tm1Alj related

Developmental Biology Research
Limb Patterning Defects
Neurodevelopmental Defects

Neurobiology Research
Neurodevelopmental Defects

Genes & Alleles

Gene & Allele Information

 
Allele Symbol En1tm1Alj
Allele Name targeted mutation 1, Alexandra L Joyner
Allele Type Targeted (knock-out)
Common Name(s) En-1hd;
Mutation Made By Alexandra Joyner,   New York University Medical Center
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl+
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name En1, engrailed 1
Chromosome 1
Gene Common Name(s) En-1; Mo-en.1; engrailed-1;
Molecular Note A neomycin selection cassette replaced 0.85 kb of exon 2, which encodes part of the homeobox domain. [MGI Ref ID J:19212]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Wurst W; Auerbach AB; Joyner AL. 1994. Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum. Development 120(7):2065-75. [PubMed: 7925010]  [MGI Ref ID J:19212]

Additional References

Hanks M; Wurst W; Anson-Cartwright L; Auerbach AB; Joyner AL. 1995. Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2 [see comments] Science 269(5224):679-82. [PubMed: 7624797]  [MGI Ref ID J:27767]

Loomis CA; Harris E; Michaud J; Wurst W; Hanks M; Joyner AL. 1996. The mouse Engrailed-1 gene and ventral limb patterning. Nature 382(6589):360-3. [PubMed: 8684466]  [MGI Ref ID J:34307]

Loomis CA; Kimmel RA; Tong CX; Michaud J; Joyner AL. 1998. Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs. Development 125(6):1137-48. [PubMed: 9463360]  [MGI Ref ID J:46971]

Matise MP; Joyner AL. 1997. Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons. J Neurosci 17(20):7805-16. [PubMed: 9315901]  [MGI Ref ID J:43464]

En1tm1Alj related

Adamska M; MacDonald BT; Sarmast ZH; Oliver ER; Meisler MH. 2004. En1 and Wnt7a interact with Dkk1 during limb development in the mouse. Dev Biol 272(1):134-44. [PubMed: 15242796]  [MGI Ref ID J:92327]

Bilovocky NA; Romito-DiGiacomo RR; Murcia CL; Maricich SM; Herrup K. 2003. Factors in the genetic background suppress the engrailed-1 cerebellar phenotype. J Neurosci 23(12):5105-12. [PubMed: 12832534]  [MGI Ref ID J:84363]

Cygan JA; Johnson RL; McMahon AP. 1997. Novel regulatory interactions revealed by studies of murine limb pattern in Wnt-7a and En-1 mutants. Development 124(24):5021-32. [PubMed: 9362463]  [MGI Ref ID J:45301]

Deckelbaum RA; Majithia A; Booker T; Henderson JE; Loomis CA. 2006. The homeoprotein engrailed 1 has pleiotropic functions in calvarial intramembranous bone formation and remodeling. Development 133(1):63-74. [PubMed: 16319118]  [MGI Ref ID J:104802]

Hanks M; Wurst W; Anson-Cartwright L; Auerbach AB; Joyner AL. 1995. Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2 [see comments] Science 269(5224):679-82. [PubMed: 7624797]  [MGI Ref ID J:27767]

Liu A; Joyner AL. 2001. EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. Development 128(2):181-91. [PubMed: 11124114]  [MGI Ref ID J:66592]

Loomis CA; Harris E; Michaud J; Wurst W; Hanks M; Joyner AL. 1996. The mouse Engrailed-1 gene and ventral limb patterning. Nature 382(6589):360-3. [PubMed: 8684466]  [MGI Ref ID J:34307]

Loomis CA; Kimmel RA; Tong CX; Michaud J; Joyner AL. 1998. Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs. Development 125(6):1137-48. [PubMed: 9463360]  [MGI Ref ID J:46971]

Louvi A; Alexandre P; Metin C; Wurst W; Wassef M. 2003. The isthmic neuroepithelium is essential for cerebellar midline fusion. Development 130(22):5319-30. [PubMed: 14507778]  [MGI Ref ID J:85727]

Matise MP; Joyner AL. 1997. Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons. J Neurosci 17(20):7805-16. [PubMed: 9315901]  [MGI Ref ID J:43464]

Murcia CL; Bilovocky NA; Herrup K. 2004. Dissecting complex genetic interactions that influence the Engrailed-1 limb phenotype. Mamm Genome 15(5):352-60. [PubMed: 15170224]  [MGI Ref ID J:90096]

Murcia CL; Gulden FO; Cherosky NA; Herrup K. 2007. A genetic study of the suppressors of the Engrailed-1 cerebellar phenotype. Brain Res 1140:170-8. [PubMed: 16884697]  [MGI Ref ID J:120598]

Simon HH; Saueressig H; Wurst W; Goulding MD; O'Leary DD. 2001. Fate of midbrain dopaminergic neurons controlled by the engrailed genes. J Neurosci 21(9):3126-34. [PubMed: 11312297]  [MGI Ref ID J:68925]

Simon HH; Scholz C; O'Leary DD. 2005. Engrailed genes control developmental fate of serotonergic and noradrenergic neurons in mid- and hindbrain in a gene dose-dependent manner. Mol Cell Neurosci 28(1):96-105. [PubMed: 15607945]  [MGI Ref ID J:95392]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Price (US dollars $)
Cryorecovery Fee $1900.00
Animals Provided

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.

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Price (US dollars $)
Cryorecovery Fee $2470.00
Animals Provided

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.

Additional Supply Details

Supply Details

Standard SupplyCryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks.

    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.

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.

General Terms and Conditions


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