B6.129P2-Lrp1tm4Ajmr/Orl

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EMMA IDEM:05273
Citation informationRRID:IMSR_EM:05273 

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International strain nameB6.129P2-Lrp1tm4Ajmr/Orl
Alternative nameLrp1 distal NPXYXXL (NPXY2) motif knock-in mutant
Strain typeTargeted Mutant Strains : Knock-in
Allele/Transgene symbolLrp1tm4Ajmr
Gene/Transgene symbolLrp1

Information from provider

ProviderAnton Roebroek
Provider affiliationHuman Genetics, K.U. Leuven
Genetic informationLrp1 knock-in mouse carrying mutant Lrp1 cDNA sequences in the 3' end of the gene replacing the corresponding genomic sequences: no intron 76 to intron 88 sequences present. The mutations are introduced to inactivate the distal NPXYXXL (NPXY2) motif in the intracellular domain of LRP1 (NPVYATL -> AAVAATL). The Lrp1 knock-in allele was generated by application of recombinase mediated cassette exchange (RMCE) in a ES cell line carrying an exchangeable cassette with a selection marker in the Lrp1 gene replacing the 3' end exons (exons 76 to 89) of the gene. By application of RMCE the Lrp1 gene was functionally restored by wild-type or mutant Lrp1 cDNA sequences resulting in a series of Lrp1 knock-in mutant alleles and mice including the Lrp1 distal NPXYXXL (NPXY2) motif knock-in mutant.
Phenotypic information1. Initial analysis (PubMed ID: 16382151): Normal phenotype: no abnormal phenotype detected: mice are fertile, viable and indistinguishable from wild-type mice. 2. Analysis of cultured primary hippocampal neurons (PubMed ID: 18321860): impairment of NMDA receptor-mediated signal transduction upon tPA stimulation. 3. Analysis after cross into LDLR-deficient background (PubMed ID: 19667105): enhanced postprandial dyslipidemia and atherosclerosis. 4. Functional analysis of immortalized MEFS (PubMed ID: 19667105 and 19856143): partial impairment of endocytic uptake of ligands. 5. Impact on plasma ApoM levels (PubMed ID: 20360257): elevated plasma ApoM levels.
Breeding historyBackcrossed 8 times to C57BL/6, only heterozygous mice available.
References
  • Mutant Lrp1 knock-in mice generated by recombinase-mediated cassette exchange reveal differential importance of the NPXY motifs in the intracellular domain of LRP1 for normal fetal development.;Roebroek Anton J M, Reekmans Sara, Lauwers Annick, Feyaerts Nathalie, Smeijers Liesbet, Hartmann Dieter, ;2006;Molecular and cellular biology;26;605-16; 16382151
  • Inactivation of the proximal NPXY motif impairs early steps in LRP1 biosynthesis.;Reekmans Sara M, Pflanzner Thorsten, Gordts Philip L S M, Isbert Simone, Zimmermann Pascale, Annaert Wim, Weggen Sascha, Roebroek Anton J M, Pietrzik Claus U, ;2010;Cellular and molecular life sciences : CMLS;67;135-45; 19856143
  • The functional role of the second NPXY motif of the LRP1 beta-chain in tissue-type plasminogen activator-mediated activation of N-methyl-D-aspartate receptors.;Martin Anne M, Kuhlmann Christoph, Trossbach Svenja, Jaeger Sebastian, Waldron Elaine, Roebroek Anton, Luhmann Heiko J, Laatsch Alexander, Weggen Sascha, Lessmann Volkmar, Pietrzik Claus U, ;2008;The Journal of biological chemistry;283;12004-13; 18321860
  • Inactivation of the LRP1 intracellular NPxYxxL motif in LDLR-deficient mice enhances postprandial dyslipidemia and atherosclerosis.;Gordts Philip L S M, Reekmans Sara, Lauwers Annick, Van Dongen Amber, Verbeek Leen, Roebroek Anton J M, ;2009;Arteriosclerosis, thrombosis, and vascular biology;29;1258-64; 19667105
  • Opposing effects of apolipoprotein m on catabolism of apolipoprotein B-containing lipoproteins and atherosclerosis.;Christoffersen Christina, Pedersen Tanja Xenia, Gordts Philip L S M, Roebroek Anton J M, Dahlbäck Björn, Nielsen Lars Bo, ;2010;Circulation research;106;1624-34; 20360257
Homozygous fertileyes
Homozygous viableyes
Homozygous matings requiredno
Immunocompromisednot known

Information from EMMA

Archiving centreCNRS-TAAM – Typing and Archiving of Animal Models, Orléans, France
Animals used for archivingheterozygous C57BL/6J males, wild-type C57BL/6J females

Disease and phenotype information

Orphanet associated rare diseases, based on orthologous gene matching

IMPC phenotypes (gene matching)
  • microphthalmia / IMPC
  • abnormal craniofacial morphology / IMPC
  • increased circulating alkaline phosphatase level / IMPC
  • abnormal embryo size / IMPC
  • abnormal limb bud morphology / IMPC
  • abnormal forebrain morphology / IMPC
  • hemorrhage / IMPC
  • preweaning lethality, complete penetrance / IMPC
  • abnormal lens morphology / IMPC
  • increased heart weight / IMPC
MGI phenotypes (gene matching)
  • abnormal liver morphology / MGI
  • decreased hepatocyte number / MGI
  • herniated abdominal wall / MGI
  • internal hemorrhage / MGI
  • no abnormal phenotype detected / MGI
  • persistent truncus arteriosis / MGI
  • omphalocele / MGI
  • liver degeneration / MGI
  • abnormal body wall morphology / MGI
  • diaphragmatic hernia / MGI
  • embryonic growth retardation / MGI
  • abnormal liver perisinusoidal space morphology / MGI
  • abnormal heart ventricle outflow tract morphology / MGI
  • atrioventricular septal defect / MGI
  • perinatal lethality, complete penetrance / MGI
  • embryonic lethality during organogenesis, complete penetrance / MGI
  • lethality throughout fetal growth and development, incomplete penetrance / MGI

Literature references

  • Mutant Lrp1 knock-in mice generated by recombinase-mediated cassette exchange reveal differential importance of the NPXY motifs in the intracellular domain of LRP1 for normal fetal development.;Roebroek Anton J M, Reekmans Sara, Lauwers Annick, Feyaerts Nathalie, Smeijers Liesbet, Hartmann Dieter, ;2006;Molecular and cellular biology;26;605-16; 16382151
  • Inactivation of the proximal NPXY motif impairs early steps in LRP1 biosynthesis.;Reekmans Sara M, Pflanzner Thorsten, Gordts Philip L S M, Isbert Simone, Zimmermann Pascale, Annaert Wim, Weggen Sascha, Roebroek Anton J M, Pietrzik Claus U, ;2010;Cellular and molecular life sciences : CMLS;67;135-45; 19856143
  • The functional role of the second NPXY motif of the LRP1 beta-chain in tissue-type plasminogen activator-mediated activation of N-methyl-D-aspartate receptors.;Martin Anne M, Kuhlmann Christoph, Trossbach Svenja, Jaeger Sebastian, Waldron Elaine, Roebroek Anton, Luhmann Heiko J, Laatsch Alexander, Weggen Sascha, Lessmann Volkmar, Pietrzik Claus U, ;2008;The Journal of biological chemistry;283;12004-13; 18321860
  • Inactivation of the LRP1 intracellular NPxYxxL motif in LDLR-deficient mice enhances postprandial dyslipidemia and atherosclerosis.;Gordts Philip L S M, Reekmans Sara, Lauwers Annick, Van Dongen Amber, Verbeek Leen, Roebroek Anton J M, ;2009;Arteriosclerosis, thrombosis, and vascular biology;29;1258-64; 19667105
  • Opposing effects of apolipoprotein m on catabolism of apolipoprotein B-containing lipoproteins and atherosclerosis.;Christoffersen Christina, Pedersen Tanja Xenia, Gordts Philip L S M, Roebroek Anton J M, Dahlbäck Björn, Nielsen Lars Bo, ;2010;Circulation research;106;1624-34; 20360257

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