Viability Primary Screen IMPC_VIA_001

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Purpose

To assess the postnatal viability, sub-viability, and lethality of homozygous mice during cohort production.

Description MP Term
Complete preweaning lethality MP:0011100
Partial preweaning lethality MP:0011110

 

Experimental Design

  • Monitor 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.  (if other breeding strategies are used specify in the metadata and follow this convention HomXHet FemaleXMale)
  • Definition of female age: "Female age earliest start/Female age oldest end" age of the youngest and oldest female mouse respectively when cohort breeding starts
  • Age to be genotyped: P1-P28
  • Record sex ratios of pups
  • Collect and report all litters and genotype data: flag strains that produce no homozygote pups
  • Identify and score lethals (defined as no homozygotes at genotype)
  • Identify subviables (defined as <50% of expected homozygotes)
  • If homozygous lethal: perform the embryonic lethal pipeline (if available)

Procedure

1.    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.
2.    Identify strains that produce no homozygous/hemizygous male or female pups.
    a.    Strains that produce NO homozygous pups will be considered LETHAL (complete preweaning lethality [MP: 0011100]).
    b.    X-linked strains that produce NO hemizygous male pups and NO female homozygous pups will be considered LETHAL (complete preweaning lethality [MP: 0011100]).
    c.    These will undergo embryonic lethal pipeline (if available)
3.    Identify strains that produce less than normal numbers of homozygous/hemizygous male or female pups.
    a.    Strains that produce <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]).
    b.    X-linked strains that produce <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  female homozygous pups will be considered SUBVIABLE (partial preweaning lethality [MP: 0011110]).
    c.    Some centers will proceed with secondary screening.
4.    For lethal and subviable strains, heterozygous progeny will be sent for adult phenotyping.
 

Notes

All genotypes should be collected using validated assays.
Line 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.
 

Sub-viable significance table:

 

Number genotyped Pups observed Formula (Excel) P-value
28 3 =BINOMDIST(3,28,0.25,1) 0.055135567
29 4 =BINOMDIST(4,29,0.25,1) 0.115324345
30 4 =BINOMDIST(4,30,0.25,1) 0.0978696
31 4 =BINOMDIST(4,31,0.25,1) 0.082764531
32 4 =BINOMDIST(4,32,0.25,1) 0.069757389
33 4 =BINOMDIST(4,33,0.25,1) 0.05860841
34 4 =BINOMDIST(4,34,0.25,1) 0.049093333
35 4 =BINOMDIST(4,35,0.25,1) 0.041005517
36 4 =BINOMDIST(4,36,0.25,1) 0.034156964
37 5 =BINOMDIST(5,37,0.25,1) 0.071139152
38 5 =BINOMDIST(5,38,0.25,1) 0.060448988
39 5 =BINOMDIST(5,39,0.25,1) 0.051216574
40 5 =BINOMDIST(5,40,0.25,1) 0.043273983
41 5 =BINOMDIST(5,41,0.25,1) 0.036466047
42 5 =BINOMDIST(5,42,0.25,1) 0.030650935
43 5 =BINOMDIST(5,43,0.25,1) 0.025700232
44 5 =BINOMDIST(5,44,0.25,1) 0.021498648
45 5 =BINOMDIST(5,45,0.25,1) 0.017943462
46 5 =BINOMDIST(5,46,0.25,1) 0.014943774
47 5 =BINOMDIST(5,47,0.25,1) 0.012419646
48 5 =BINOMDIST(5,48,0.25,1) 0.010301181
49 5 =BINOMDIST(5,49,0.25,1) 0.008527583
50 5 =BINOMDIST(5,50,0.25,1) 0.007046225
51 5 =BINOMDIST(5,51,0.25,1) 0.005811761
52 5 =BINOMDIST(5,52,0.25,1) 0.004785276

 

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