We modeled the NPARM case in vivo by generating a cognate conditional transgenic mouse line.
This implies that, for each element, by generating a sample from the conditional, we can generate a sample from.
Due to the early embryonic lethality of Wnt7b mutants, Stenman and colleagues used a conditional approach by generating a mouse line with null alleles of Wnt7a and loxp flanked Wnt7b alleles in conjunction with a Nestin-Cre to delete Wnt7b in the developing neuroepithelium [ 96].
This integration is approximated by generating a large number of random ARGs conditional on the demographic model and averaging the likelihoods computed over this sample of ARGs.
Using SLINK, replicates were generated for each given pedigree structure conditional on affection status by generating a marker with a minor allele frequency of 0.0001 completely linked (recombination fraction =0.0) to a fully penetrant autosomal recessive disease locus with an allele frequency of 0.0001.
To investigate the in vivo function of Cobra1, we generated a conditional KO mouse by bracketing the putative promoter and the first four exons of the gene with loxP sites (Fig. 1A).
To decipher the different roles of Rfx6, we generated a conditional knockout mouse by flanking exon 3, which encodes a part of the DNA binding domain, by two loxP sites, generating a null allele.
To address the role of mesenchymal BMP signaling in craniofacial development, we generated a conditional knockdown mouse by expressing the dominant-negative Bmpr1a in NC-derived cells expressing the myelin protein zero(Mpz)- Cre transgene.
In addition, we generated a conditional PMR1 mutant by replacement of the promoter region of PMR1 with a tetO promoter that is active in the absence of doxycycline and prevents gene expression upon addition of 10 μg/ml of the chemical.
In order to investigate the physiological function of Fto in mice, we generated a conditional knockout (cko) line by flanking exon 3 with two loxP sites (Figure 2A).
