These FE65L1 mutant mice, along with FE65 mutant mice, may be useful in studying brain development (neuronal positioning and establishment of axonal projections) and abnormal brain morphology (Cobblestone Lissencephaly, marginal zone heterotopias, and pial basement membrane integrity); as well as the function of FE65 family proteins in amyloid precursor protein (APP) processing, Alzheimer's disease, and neuronal protein trafficking.
Dr. Joachim Herz, Univ of Texas Southwest Med Ctr Dallas
The FE65L1 knockout allele has a tau-lacZ fusion protein replacing exon 4 of the Apbb2 gene. No protein expression is detected from the mutant locus, and the donating investigator reports that whether lacZ staining faithfully reflects FE65L1 expression has not been conclusively resolved. Homozygous (FE65L1-/-) mice are viable, fertile, and indistinguishable from wildtype littermates. Histological examination of adult brains shows no obvious neuroanatomical abnormalities. These FE65L1 mutant mice may be useful in studying brain development (neuronal positioning and establishment of axonal projections) and abnormal brain morphology (Cobblestone Lissencephaly, marginal zone heterotopias, and pial basement membrane integrity); as well as the function of FE65 family proteins in amyloid precursor protein (APP) processing, Alzheimer's disease, and neuronal protein trafficking.
For example, mice homozygous for both this FE65L1 knockout allele and the FE65 knockout allele (see Stock No. 012865) exhibit postnatal lethality (partial penetrance), are smaller than their wildtype or heterozygous littermates, and often display bilateral circling. While routine histological staining of the major organs in double knockout (FE65-/-;FE65L1-/-) mice reveals no overt anatomical abnormalities, FE65-/-;FE65L1-/- mice display cortical dysplasia with heterotopias resembling those of Cobblestone Lissencephaly. Specifically, FE65-/-;FE65L1-/- mice exhibit neuroanatomical abnormalities in the cortex and hippocampus that include marginal zone heterotopias (migration of heterotopic neurons beyond the marginal zone and located in the wrong part of the brain), midline crossing defects, and axonal pathfinding abnormalities. The phenotype of FE65-/-;FE65L1-/- mice shares remarkable similarities with that reported for mutant mice lacking FE65-binding partners, the three members of the APP gene family (APP, APLP1 and APLP2), and the Ena/Vasp protein family.
These FE65L1 mutant mice were created in the laboratory of Dr. Joachim Herz (University of Texas Southwestern Medical Center, Dallas). A targeting vector was designed to replace 692 nucleotides of exon 4 of the FE65L1 (Apbb2) locus with a tau::β-galactosidase (tau-lacZ) fusion protein and oppositely-oriented neo cassette. This construct was electroporated into 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6J inbred females to establish the colony. Mutant mice were then bred together for several generations and made homozygous. Therefore, homozygous mice on a mixed C57BL/6J;129SvEvTac genetic background (not C57BL/6;129SvEvBradley as originally reported) were sent to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Joachim Herz|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Apbb2tm1Sgnt; Fe65l1-|
|Gene Symbol and Name||Apbb2, amyloid beta (A4) precursor protein-binding, family B, member 2|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A targeting vector was designed to replace 692 nucleotides of exon 4 with a tau-LacZ fusion protein and a neo cassette. Protein was not detected by Western blot analysis.|
|Mutations Made By|| |
Dr. Joachim Herz, Univ of Texas Southwest Med Ctr Dallas
When maintaining a live colony, homozygous mice may be bred together.
When using the B6;129S6-Apbb2tm1Her/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012869 in your Materials and Methods section.
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