{"Procedure":"<p>\t1.&nbsp;&nbsp; &nbsp;Monitor pup number, genotypes and sex ratios of Het X Het intercrosses set to generate cohorts for phenotyping. Score at least 28 live pups when genotyped, unless four or more hom pups are produced before this threshold is reached.<br />\t2.&nbsp;&nbsp; &nbsp;Identify strains that produce no homozygous/hemizygous male or female pups.<br />\t&nbsp;&nbsp;&nbsp; a.&nbsp;&nbsp; &nbsp;Strains that produce NO homozygous pups will be considered LETHAL (complete preweaning lethality [MP: 0011100]).<br />\t&nbsp;&nbsp;&nbsp; b.&nbsp;&nbsp; &nbsp;X-linked strains that produce NO hemizygous male pups and NO female homozygous pups will be considered LETHAL (complete preweaning lethality [MP: 0011100]).<br />\t&nbsp;&nbsp;&nbsp; c.&nbsp;&nbsp; &nbsp;These will undergo embryonic lethal pipeline (if available)<br />\t3.&nbsp;&nbsp; &nbsp;Identify strains that produce less than normal numbers of homozygous/hemizygous male or female pups.<br />\t&nbsp;&nbsp;&nbsp; a.&nbsp;&nbsp; &nbsp;Strains that produce &lt;50% expected (#totalpups * 0.125 (3 for 28) (4 for 29-36) (5 for 37-52) (See stats table in Notes)) homozygous pups will be considered SUBVIABLE (partial preweaning lethality [MP: 0011110]).<br />\t&nbsp;&nbsp;&nbsp; b.&nbsp;&nbsp; &nbsp;X-linked strains that produce &lt;50% expected (#total pups* 0.125 (3 for 28) (4 for 29-36) (5 for 37-52) (See stats table in Notes)) hemizygous male pups and&nbsp; female homozygous pups will be considered SUBVIABLE (partial preweaning lethality [MP: 0011110]).<br />\t&nbsp;&nbsp;&nbsp; c.&nbsp;&nbsp; &nbsp;Some centers will proceed with secondary screening.<br />\t4.&nbsp;&nbsp; &nbsp;For lethal and subviable strains, heterozygous progeny will be sent for adult phenotyping.<br />\t&nbsp;</p>","Purpose":"<p>\tTo assess the postnatal viability, sub-viability, and lethality of homozygous mice during cohort production.","Experimental Design":"<ul>\t<li>\t\tMonitor genotypes of Het X Het breeding units; score genotypes of at least 28 live pups, unless four or more hom pups are produced before this threshold is reached.&nbsp; (if other breeding strategies are used specify in the metadata and follow this convention HomXHet FemaleXMale)</li>\t<li>\t\tDefinition of female age: &quot;Female age earliest start/Female age oldest end&quot; age of the youngest and oldest female mouse respectively when cohort breeding starts</li>\t<li>\t\tAge to be genotyped: P1-P28</li>\t<li>\t\tRecord sex ratios of pups</li>\t<li>\t\tCollect and report all litters and genotype data: flag strains that produce no homozygote pups</li>\t<li>\t\tIdentify and score lethals (defined as no homozygotes at genotype)</li>\t<li>\t\tIdentify subviables (defined as &lt;50% of expected homozygotes)</li>\t<li>\t\tIf homozygous lethal: perform the embryonic lethal pipeline (if available)</li></ul>","Notes":"<p>\tAll genotypes should be collected using validated assays.<br />\tLine level calls will be rejected until 28 mice have been genotyped, unless four or more hom pups are produced before this threshold is reached, in which case a viable call is valid.<br />\t&nbsp;</p><p>\tSub-viable significance table:</p><p>\t&nbsp;</p><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:600px !important;\" width=\"600\">\t\t<tr>\t\t\t<td><span style=\"font-size:10px;\">Number genotyped</span>\t\t\t</td>\t\t\t<td><span style=\"font-size:10px;\">Pups observed</span>\t\t\t</td>\t\t\t<td><span style=\"font-size:10px;\">Formula (Excel)</span>\t\t\t</td>\t\t\t<td><span style=\"font-size:10px;\">P-value</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td><span style=\"font-size:10px;\">28</span>\t\t\t</td>\t\t\t<td><span style=\"font-size:10px;\">3</span>\t\t\t</td>\t\t\t<td><span style=\"font-size:10px;\">=BINOMDIST(3,28,0.25,1)</span>\t\t\t</td>\t\t\t<td>0.055135567</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td><span style=\"font-size:10px;\">29</span>\t\t\t</td>\t\t\t<td><span style=\"font-size:10px;\">4</span>\t\t\t</td>\t\t\t<td><span style=\"font-size:10px;\">=BINOMDIST(4,29,0.25,1)</span>\t\t\t</td>\t\t\t<td><span style=\"font-size:10px;\">0.115324345</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">30</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">4</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(4,30,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.0978696</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">31</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">4</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(4,31,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.082764531</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">32</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">4</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(4,32,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.069757389</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">33</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">4</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(4,33,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.05860841</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">34</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">4</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(4,34,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.049093333</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">35</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">4</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(4,35,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.041005517</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">36</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">4</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(4,36,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.034156964</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">37</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,37,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.071139152</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">38</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,38,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.060448988</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">39</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,39,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.051216574</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">40</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,40,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.043273983</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">41</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,41,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.036466047</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">42</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,42,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.030650935</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">43</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,43,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.025700232</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">44</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,44,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.021498648</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">45</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,45,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.017943462</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">46</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,46,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.014943774</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">47</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,47,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.012419646</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">48</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,48,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.010301181</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">49</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,49,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.008527583</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">50</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,50,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.007046225</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">51</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,51,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.005811761</span>\t\t\t</td>\t\t</tr>\t\t<tr>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">52</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">5</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">=BINOMDIST(5,52,0.25,1)</span>\t\t\t</td>\t\t\t<td>\t\t\t\t\t\t\t\t\t<span style=\"font-size:10px;\">0.004785276</span>\t\t\t</td>\t\t</tr></table><p>\t&nbsp;</p>"}