B6.129-Fbn1^tm1Hcd/J

Stock number: 012885
Product name: Fbn1^C1039G
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Mouse/Human Gene Homologs

Description

These mice harbor a p.Cys1041Gly mutation in the Fbn1 (fibrillin 1) gene similar to that which causes classic manifestations of Marfan syndrome in humans (Cys1039Tyr). Heterozygous mice develop proximal aortic aneurysms, mitral valve thickenings, pulmonary alveolar septation defects, mild thoracic kyphosis, and skeletal myopathy, but 90% reportedly live to one year of age.

Detailed description

Mice homozygous for this Fbn1 (fibrillin 1) Cys1041Gly missense mutation (previously identified as Cys1039Gly) are small and die before two weeks of age. A similar mutation in man (Cys1039Tyr) is known to cause classic manifestations of Marfan syndrome in humans. Heterozygous mice develop proximal aortic aneurysms, mitral valve thickenings, pulmonary alveolar septation defects, mild thoracic kyphosis, and skeletal myopathy, but 90% reportedly live to one year of age.

Development

Site-directed mutagenesis was used to create a single G->T base pair alteration in the mouse gene resulting in a Cys->Gly change at amino acid 1041 (previously identified in the literature as C1039G). This corresponds with the human C1039Y mutation. The mutation was created in (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. A loxP-flanked neomycin resistance cassette placed in intron 24 was excised through a cross with a CMV-cre mouse. This strain was backcrossed to C57BL/6 for more than nine generations by the donating laboratory.

Allele

Symbol: Fbn1^tm1Hcd
Name: targeted mutation 1, Harry C Dietz
MGI accession ID: MGI:3690325
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: Fbn1^C1037G; Fbn1^C1039G; Fbn1^C1041G
Marker symbol: Fbn1
Marker name: fibrillin 1
Marker synonyms: ACMICD; ECTOL1; FBN; Fib-1; GPHYSD2; MASS; MFLS; MFS1; OCTD; SGS; SSKS; WMS; WMS2
Chromosome: 2
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Site-directed mutagenesis creates a single T to G base pair alteration in the mouse gene resulting in a Cys to Gly change at amino acid 1041 (previously identified in the literature as C1039G and C1037G). This corresponds with the human C1039Y mutation. The floxed neo selection cassette was removed by crossing to a ubiquitously expressing Cre mouse line.