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I am reading a journal paper and I have come across the following statement:

To investigate this, $CHL1^{−/−}$ / $L1^{−/y}$ double mutant mice were generated and analyzed for thalamocortical axon topography.

I know that -/- means knockout, +/- means heterozygous and +/+ means wild-type. But what does -/y mean? I have never seen this notation before.

Any insights are appreciated.

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According to the introduction, human L1 is located at Xq28, in the q arm of the X chromosome. It is also on the mouse X chromosome. The $CHL1^{-/-}$ nomenclature you've already figured out: a homozygous knockout of the CHL1 gene. I haven't thoroughly read the whole paper, but there must be some undesirable phenotype when L1 is homozygously knocked out in female (X/X) mice, so the researchers in this paper are using male (X/Y) mice, with L1 knocked out on the single X chromosome. There is no corresponding allele on the Y chromosome, so the nomenclature is $L1^{-/y}$.

This is borne out in the Materials and Methods:

The L1 gene is located on the X chromosome, and its deletion results in poor breeding capability of males and thus female mice homozygous null for the CHL1 gene and heterozygous for L1 ($CHL1^{-/-}$/$L1^{+/-}$; C57BL/6/Sv129, ∼9:1) were crossed with $CHL1^{-/-}$/$L1^{+/y}$ males (C57BL/6) to produce $CHL1^{-/-}$/$L1^{-/y}$ double mutants.

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  • $\begingroup$ From their methods as you've quoted it seems that the issue is that the male L1 knockouts don't breed well; that makes it difficult (perhaps impossible?) to produce a female with both copies knocked out, because one of those has to come from the male-that-doesn't-breed-well. There may not be an known undesirable phenotype for the female double knockouts, just that there's no way to produce them by breeding, and it's much easier to just genotype the male offspring. $\endgroup$
    – Bryan Krause
    Jan 26 at 20:35
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    $\begingroup$ I read that section from the M&Ms multiple times, and I still couldn't figure out exactly what the issue was. You finally broke through my brain fog, thanks :) $\endgroup$
    – MattDMo
    Jan 26 at 20:41
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    $\begingroup$ Took me a second too... my first thought was they were just using male mice for other convenience reasons; it's been fairly common in neuroscience to use only male rodents to reduce variance in measurements from sex differences and estrous cycle, though there's a bit of a push against that trend these days. $\endgroup$
    – Bryan Krause
    Jan 26 at 20:44

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