Preweanling sensorial and motor development in laboratory mice: Quantitative Trait Loci mapping

Chromosomal mapping of genes linked with 19 measures of sensorial, motor, a nd body weight development were investigated. Chromosomal mapping is the fi rst step towards gene identification. When a genomic region is shown to be linked to a trait, it is possible to select a reduced number of candidate g enes that have been previously mapped on this region. The involvement of ev ery gene can be individually tested either by molecular (transgenesis, homo logous recombination) ol traditional methods (congenicity). Mapping was per formed using 389 males and females from two inbred strains of laboratory mi ce C57BL/6By and NZB/BINJ, their reciprocal F(1)s and F(2)s. Thirty-six Qua ntitative Trait Loci (QTL) were mapped, 12 reached the 3.23 lod score, bein g thus considered as confirmed. These QTL were tentatively labeled: Cliff D rop Aversion (Cliff Qtl), Geotaxia (Geot Qtl), Vertical Clinging (VertCling Qtl), Bar Holding with the 4 paws (BH4P Qtl), Age at Eyelid Opening (Aeyo Qtl), Visual Placing (Vispl Qtl), Startle Response (Start Qtl1, Start Qtl2) , Body Weight at Day 10 in Males pooled with Females (Bwefmd10 Qtl), and Bo dy Weight at Day 30 in males (Bwemd30 Qtl). For the majority of the develop mental measures, the QTL that were mapped contributed little to the phenoty pic variance, even when mitochondrial DNA contribution was included: Righti ng Response (12.7%), Cliff Drop Aversion (10%), Crossed Extensor Response ( 18.1%), Geotaxia (16.2%), Bar Holding Response for 10 s (12.1%), Bar Holdin g Response with 4 paws (8.1%), Vertical Clinging (9.3%), Vertical Climbing (5%), Startle Response (21.2%), Eyelid Opening (14.6%), Visual Placing (22% ), Body Weight at Day 10 (27%), Body Weight at Day 15 in Females (52.5%), B ody Weight at Day 15 in Males (17%), Body Weight at Day 30 in Females (42%) , and Body Weight at Day 30 in Males (48%). A factorial analysis of the cor relations between the measures of development did not provide evidence of a general factor. A general genetic factor of development was also rejected because few common genetic correlates were discovered for the 19 measures o f development (Body Weight at Days 15 and 30 in Females on Chromosome 2, Ey elid Opening and Body Weight at Day 10 on Chromosome 5 and mitochondrial ge nome for five measures). Co-identification of genes, the function of which were previously known thanks to newly discovered QTL, should help to explai n the function of QTL. Present data help to highlight candidate regions inc luding several genes that could be candidates for the QTL function. Large c onfidence intervals were obtained as usual from the F-2 intercrossed popula tion. More stringent methods are suggested for more efficient co-identifica tion. (C) 1999 John Wiley & Sons, Inc.