Tests of Genetic Allelism between Four Inbred Mouse Strains with Absent Corpus Callosum

Abstract

Abstract:Inbred mouse strains that lack the corpus callosum connecting the cerebral hemispheres in the adult differ from the C57BL/6J strain at several relevant but unknown loci. To identify at least one major locus that influences axon guidance, different strains showing phenotypically similar defects were crossed to test for allelism. It the F 1 hybrid between two strains with the same brain defect is phenotypically normal, it is much more likely that the two strains will differ at fewer loci than will an acallosal strain and C57BL/6J. This approach proved to be very informative. Five reasonable models of inheritance involving two or three loci were assessed, and the data justified rejection of all but one hypothesis. A total of 479 mice were obtained from tour inbred strains prone to absence of the corpus callosum (BALB/cWah 1, BALB/cWah2,

Survey of 21 inbred mouse strains in two laboratories reveals that BTBR T/+ tf/tf has severely reduced hippocampal commissure and absent corpus callosum

“…4. As observed previously with other strains and crosses [8,22], the HC was abnormally small only when the CC was totally absent. The distribution of phenotypes for 9XCA×BTBR was almost the same as for BTBR itself; only three of 16 mice of this hybrid cross had an HC size in the normal range and one had a few CC axons crossing to the opposite hemisphere (CC index of abnormality = 0.07).…”

“…Because the crosses of BTBR with either progenitor strain BALB/ cWah1 or 129P3/ReJ are much less severely afflicted than BTBR, the data support a model involving a difference between BALB/c and 129 progenitors at two major loci, where BALB/c has the recessive allele at one locus and 129 is recessive at the other locus [8,22]. According to this model, being homozygous recessive at just one of the loci produces mice showing incomplete penetrance for CC defects, whereas being homozygous recessive at both loci creates complete penetrance for a much more severe defect, total CC absence and reduced HC.…”

“…The distribution of phenotypes for 9XCA×BTBR was almost the same as for BTBR itself; only three of 16 mice of this hybrid cross had an HC size in the normal range and one had a few CC axons crossing to the opposite hemisphere (CC index of abnormality = 0.07). When BTBR was crossed to the progenitors of the 9XCA strain, however, phenotypes were very similar to those of the 129P1 /ReJ and BALB/cWah1 strains [8,23].…”

“…Every BALB/c and 129-derived strain examined to date shows incomplete penetrance for the CC defect, whereas all I/LnJ mice suffer absent CC. About half of I/LnJ mice also exhibit severe reduction of the size of the hippocampal commissure (HC), a defect that is only seen in individuals lacking the CC [8]. The recombinant inbred strain 9XCA/Wah derived from the progenitors 129P1/ReJ and BALB/cWah1 has 100% total absence of the CC and severe reduction of the HC [23].…”

Brain studies of mouse models for neurogenetic disorders using in vivo magnetic resonance imaging (MRI)

“…It is well established that genetic background may have a profound influence on the various genetic manipulations in mice. 19 For example, deletion of the hypoxanthine phosphoribosyl-transferase (HPRT) results in Lesch-Nyhan disease in man but has no apparent effect in mice. 20 Some patients with X-linked hydrocephalus show major enlargement of the ventricular system (Figure 1), while other members of the same family may show only a very limited enlargement as a consequence of the same L1CAM mutation.…”