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We have previously engineered an animal model of PDDR by targeted inactivation of the 1α-OHase gene in mice (Endocrinology 142 (2001 31355).
We show here, by targeted inactivation of this key cohesin component in mice, that Rad21 is a DNA-damage response gene that markedly affects animal and cell survival.
The Fg-deficient mice used here were generated by targeted inactivation of the murine Fg γ chain [34], followed by crossbreeding of the resulting C57Bl/6 mice for 10 generations with Balb/c mice.
It is required for normal bone homeostasis because mice with impaired DAP12 function, either by targeted inactivation of the ITAM domain or through its complete deletion, develop osteopetrosis after puberty due to the inability of osteoclasts to resorb bone.
RFC1 knockout mice were generated by targeted inactivation of the RFC1 (Slc19allelelele as previously described [ 77].
Considerable improvement of both yield and productivity was achieved by targeted inactivation of hpd, the first gene of the homogentisate pathway.
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However, these previous studies only compared the expression profiles of drug-resistant and drug-sensitive cells or tissues, without functional validation documenting the cellular consequences induced by targeted inactivation or re-expression of candidate miRNAs.
Availability of the heterologous expression system and the natural producer strain SBCb004 provided a platform for the functional investigation of various biosynthetic genes by targeted inactivation.
Of these subunit genes, α-ENaC appears to be critical to overall salt balance, as evidenced by the severe renal salt wasting exhibited by mice with targeted inactivation of α-ENaC in the CNT (connecting tubule)/CD [ 2]. α-ENaC is also a molecular target for aldosterone.
The importance of both of these pathways is stressed by the fact that targeted inactivation of either Pcyt2, the gene coding for the rate-limiting enzyme of the Kennedy pathway, or Pisd, the gene coding for PS decarboxylase, leads to embryonic death in mice [46,47].
As an alternative, we outline the use of in vivo single node perturbations – by way of mouse models with targeted inactivation of specific loci – followed by gene and protein expression analysis to gauge systems-level effects.
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