<i>Deaf11</i> and <i>Deaf13</i> cochlear hair cells are morphologically abnormal.

<p>Middle cochlear turn sections at 8 weeks of age; Upper panels 100x magnification, scale bar 200 µm; Lower panels 400x magnification, scale bar 50 µm; <b>A</b>, <b>D</b>) <i>Atp2b2</i>^<i>+/+</i><b>B</b>, <b>E</b>) <i>Atp2b2</i>^{<i>Deaf11/Deaf11</i>}<b>C</b>, <b>F</b>) <i>Atp2b2</i>^{<i>Deaf13/Deaf13</i>}; White arrowheads point to inner hair cells; Black arrowheads point to outer hair cells; Each section is representative of 4 cochleae.</p

The <i>Deaf11</i> mutation is linked to chromosome 6.

<p>A <i>Deaf11/Deaf11</i> BALB/c mouse was crossed to a <i>+/+</i> C57BL/6 mouse and the offspring intercrossed to generate 87 N ₁F₁ mice. Mice were divided into those with a click ABR threshold ≤55 dB SPL on left (<i>+/+</i> or <i>+/Deaf11</i>) and those with a threshold ≥75 dB SPL on right (<i>Deaf11/Deaf11</i>). All mice were genotyped for SNPs on chromosome 6. SNP names and locations are listed on the left and right respectively (assembly GpCm38, database SNP, <a href="http://www.ncbi.nlm.nih.gov/projects/snp/" target="_blank">http://www.ncbi.nlm.nih.gov/projects/SNP/</a>). The numbers of mice displaying each haplotype are listed below. Informative recombinations indicate that the <i>Deaf11</i> causative mutation lies between rs13478976 at 112 Mb and rs3152403 at 121 Mb. <i>Atp2b2</i> is located at 113 Mb.</p

<i>Deaf11</i> and <i>Deaf13</i> mice display hearing loss.

<p>Mean ABR thresholds at <b>A</b>) 4 and <b>B</b>) 8 weeks of age; <i>Atp2b2</i>^<i>+/+</i> n=3 female (F), 6 male (M) at 4 wks, n = 4F, 5M at 8 wks, <i>Atp2b2</i>^{<i>+/Deaf11</i>} n = 6F, 2M at 4 wks, n = 7F, 4M at 8 wks, <i>Atp2b2</i>^{<i>+/Deaf13</i>} n = 7F, 10M at 4 wks, n = 5F, 9M at 8 wks, <i>Atp2b2</i>^{<i>Deaf11/Deaf11</i>} n = 3F, 6M at 4 wks, n = 2F and 5M at 8 wks, <i>Atp2b2</i>^{<i>Deaf13/Deaf13</i>} n = 2F, 4M, <i>Atp2b2</i>^{<i>Deaf11/Deaf13</i>} n = 4F, 3M; * p<0.01 versus <i>Atp2b2</i>^<i>+/+</i>; Error bars show standard deviation.</p

Values of absolute random loss rate (fixed requirement for platelets), extracted from the same fits of the DLS model to survival data as illustrated in <b>Figure 3</b>.

<p>1000 Monte Carlo simulations were performed and fit to obtain parameters – box-and-whisker plots indicate median, interquartile range, 2.5 and 97.5 percentiles, and outliers are plotted as individual dots.</p

Platelet counts (±standard error of the mean, s.e.m.) and best-fit LS model parameters from fits to population survival data for each genotype, with 95% C.I.'s from the Monte Carlo technique in brackets.

<p>Platelet counts (±standard error of the mean, s.e.m.) and best-fit LS model parameters from fits to population survival data for each genotype, with 95% C.I.'s from the Monte Carlo technique in brackets.</p

F-test to compare best fits with the LS model (the null hypothesis) versus the DLS model (one extra parameter – the alternative hypothesis).

<p>F-test to compare best fits with the LS model (the null hypothesis) versus the DLS model (one extra parameter – the alternative hypothesis).</p

F-test to compare best fits with the Dornhorst model (the null hypothesis) versus the DLS model (one extra parameter – the alternative hypothesis).

<p>F-test to compare best fits with the Dornhorst model (the null hypothesis) versus the DLS model (one extra parameter – the alternative hypothesis).</p

Lognormal-Senescent model fits of platelet survival data.

<p>(<b>A</b>) Population survival data and LS model best fits for <i>Bcl-x^+/Plt20</i> (blue), wild-type (green) and <i>Bak^−/−</i> (red) mice. A Monte Carlo technique was used to generate estimates of confidence intervals for the model parameters – (<b>B</b>) mean natural life span, <i>μ</i>, (<b>C</b>) standard deviation of natural life span, <i>σ</i>, (<b>D</b>) random loss rate constant, <i>r</i> (always 0 hr⁻¹ for this model), and (<b>E</b>) random loss fraction, <i>f</i> (always 0 for this model). 1000 Monte Carlo simulations were performed and fit to obtain parameters – box-and-whisker plots indicate median, interquartile range, 2.5 and 97.5 percentiles, and outliers are plotted as individual dots.</p

Dornhorst-Lognormal-Senescent model fits of platelet survival data reveals a smaller random loss fraction than the classic Dornhorst model but wide confidence intervals.

<p>(<b>A</b>) Population survival data and DLS model best fits for <i>Bcl-x^+/Plt20</i> (blue), wild-type (green) and <i>Bak^−/−</i> (red) mice. A Monte Carlo technique was used to generate estimates of confidence intervals for the model parameters – (<b>B</b>) natural life span, <i>T</i>, (<b>C</b>) standard deviation of natural life span, (<b>D</b>) random loss rate constant, <i>r</i>, and (<b>E</b>) random loss fraction, <i>f</i>. 1000 Monte Carlo simulations were performed and fit to obtain parameters – box-and-whisker plots indicate median, interquartile range, 2.5 and 97.5 percentiles, and outliers are plotted as individual dots.</p

Dornhorst model fits of platelet survival data predict that a large proportion of platelets are destroyed randomly.

<p>(<b>A</b>) Population survival data and Dornhorst model best fits for <i>Bcl-x^+/Plt20</i> (blue), wild-type (green) and <i>Bak^−/−</i> (red) mice. A Monte Carlo technique was used to generate estimates of confidence intervals for the model parameters – (<b>B</b>) natural life span, <i>T</i>, (<b>C</b>) standard deviation of natural life span (always 0 hr for this model), (<b>D</b>) random loss rate constant, <i>r</i>, and (<b>E</b>) random loss fraction, <i>f</i>. 1000 Monte Carlo simulations were performed and fit to obtain parameters – box-and-whisker plots indicate median, interquartile range, 2.5 and 97.5 percentiles, and outliers are plotted as individual dots.</p