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US6087555A Expired / Lapsed US ⏱️ 0.0 years remaining

Mice lacking expression of osteoprotegerin

Assignee: Amgen Inc
•
Filing: 1997-10-15
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Granted: 2000-07-11
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Expires: 2017-10-15
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Abstract

Abstract Disclosed is a mouse in which expression of the gene encoding Osteoprotegerin is suppressed. Also disclosed is a nucleic acid construct useful in preparing such a mouse, and a cell line containing such construct.

Inventors

  • 👤 Colin Dunstan
  • 👤 Scott Simonet
  • 👤 Ildiko Sarosi

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 12:54
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/63; C12N15/79; C12N15/85; C12N15/8509; A; A01; A01K; A01K67/00; A01K67/027; A01K67/0275; A01K67/0276; C07; C07K; C07K14/00; C07K14/435; C07K14/705; C07K14/70578; A01K2217/00; A01K2217/05; A01K2217/07; A01K2217/075; A01K2227/00; A01K2227/10; A01K2227/105; A01K2267/00; A01K2267/03

Claims Analysis

Total Claims: 10
Claim 1
Independent Claim 43 words
A transgenic mouse whose genome comprises a disruption of the endogenous osteoprotegerin (OPG) gene, wherein said disruption comprises the insertion of a selectable marker sequence, and wherein said disruption results in said mouse exhibiting decreased bone density as compared to a wild-type mouse.
Claim 2
Dependent Claim 43 words
A transgenic mouse whose genome comprises a disruption of the endogenous osteoprotegerin (OPG) gene, wherein said disruption comprises the insertion of a selectable marker sequence, and wherein said disruption results in said mouse exhibiting decreased bone density as compared to a wild-type mouse.
Claim 3
Dependent Claim 13 words
The transgenic mouse of claim 1, wherein said disruption is a homozygous disruption.
Claim 4
Dependent Claim 22 words
The transgenic mouse of claim 2, wherein said homozygous disruption results in a null mutation of the endogenous gene encoding osteoprotegerin (OPG).
Claim 5
Dependent Claim 74 words
An isolated nucleic acid comprising an osteoprotegerin (OPG) knockout construct comprising a selectable marker sequence flanked by DNA sequences homologous to the endogenous OPG gene, wherein when said construct is introduced into a mouse or an ancestor of said mouse at an embryonic stage, said selectable marker sequence disrupts the endogenous OPG gene in the genome of said mouse such that said mouse exhibits decreased bone density as compared to a wild type mouse.
Claim 6
Dependent Claim 74 words
An isolated nucleic acid comprising an osteoprotegerin (OPG) knockout construct comprising a selectable marker sequence flanked by DNA sequences homologous to the endogenous OPG gene, wherein when said construct is introduced into a mouse or an ancestor of said mouse at an embryonic stage, said selectable marker sequence disrupts the endogenous OPG gene in the genome of said mouse such that said mouse exhibits decreased bone density as compared to a wild type mouse.
Claim 7
Dependent Claim 9 words
A vector comprising the nucleic acid of claim 4.
Claim 8
Dependent Claim 16 words
A mouse RW4 embryonic stem cell line comprising the osteoprotegerin (OPG) knockout construct of claim 4.
Claim 9
Dependent Claim 47 words
A method of screening compounds that modulate bone resorption comprising introducing a compound into the mouse of claim 1 and determining the increase or decrease in bone resorption of said mouse as compared to the bone resorption of said mouse prior to the administration of the compound.
Claim 10
Dependent Claim 71 words
The osteoprotegerin (OPG) knockout construct according to claim 4, wherein said construct comprises from 5' to 3', the OPG genomic fragment 3 which is a XmnI/XmnI subfragment of a portion of exon 1 and most of exon 2, the neo cassette, OPG genomic fragment 2 which is an EcoRI/EcoRI fragment of the 3' portion of exon 2, intron 2, extron 3, and most of intron 3, and the thymidine kinase cassette.

References Cited (Backward Citations)

EP0816380A1 Cited
WO1997023614A1 Cited
EP0784093A1 Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 2003-07-11 2004-01-10 2004-07-11 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2007-07-11 2008-01-10 2008-07-11 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2011-07-11 2012-01-10 2012-07-11 $7700.00 Window Closed / Lapsed

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