GDNF Expression differs in mesenteric artery and vein

1
The Effect of Fraternal Birth Order on Motor
Coordination Developing a Model for Autism,
Attention Deficit/Hyperactivity Disorder, and
Dyslexia Allison Shaw and S. Marc Breedlove,
Ph.D., Neuroscience Program and Department of
Psychology, Michigan State University, East
Lansing, MI 48824
Background
Methods (Contd)
Current/Future Research

• Behavioral Test (Static Rod)
• Mice were tested on five static rods (69.5mm
  length), which decreased in diameter (31.1, 25.6,
  19.5, 15.4, 9.4mm), in order to assess motor
  coordination.
• Each mouse was placed with their nose facing the
  end of the rod.
• The duration it took the mouse to turn 180
  degrees (rotate) and the time it took for the
  mouses nose to cross a predetermined mark 10cm
  from the wall (transit) were recorded.
• Mice were allowed to attempt both behaviors for
  up to three minutes (180 seconds).
• If the mouse fell off of the static rod, then
  they were given a default time of 180 seconds.

• Neurodevelopmental Disorders are a broad class of
  psychiatric disorders where symptoms begin to
  appear early in development.
• Vincent et al.1 (2002) and Dalton et al.2 (2003)
  posit that some neurodevelopmental disorders
  (autism and dyslexia) may be caused by a process
  by which antibodies that transfer through the
  placenta to the fetus and affect development,
  known as the maternal immune transfer.
• Similarly, Blanchard Bogaert (1996) suggest
  that fraternal birth order may effect fetal
  development in a similar maternal transfer,
  maternal immune hypothesis, which they believe
  signals an increased androgen release.
• Autism (Cohen-Baron, unpub.) and Dyslexia (Caspi,
  unpub.) have a fraternal birth order effect.
• Males with Attention Deficit/Hyperactivity
  Disorder (inattention) have been shown to be
  hypermasculinized in finger ratio lengths due to
  prenatal androgens, as suggested by the maternal
  immune hypothesis (McFadden, in press).
• Individuals with these disorders have decreased
  motor coordination ranging from inability to
  control movement to deficiencies in fine motor
  movement.

• Current cohort of mice have been tested on a Gap
  Detection Paradigm. This test mimics that of
  tests administered to humans that are used to
  diagnose dyslexic individuals. Those with
  dyslexia have a difficult time with auditory
  processing. Results of that test have found that
  males with older brothers have a more difficult
  time detecting gaps in tones than mice with older
  sisters however, female mice seem not to be
  affected either way.
• Also, these mice have been tested in an Open
  Field Object Recognition and Novelty test. This
  paradigm will allow us to conclude whether or not
  fraternal birth order has an effect on object
  recognition. Individuals with autism have a
  difficult time with social and object
  recognition.
• Future tests include, but not limited to,
  Olfactory Recognition, partner preference, and
  sexual behaviors.
• Furthermore, a new cohort of mice will be breed
  in order to better control for variability.
• In addition to mouse model research, research
  done on humans will be included. Male/Female
  twins will be used in order to further explore
  why female mice might be affected by fraternal
  birth order. Fraternal birth order may not affect
  females, but rather her male littermates who in
  turn affect their sister.

Results
Table 1 Rotation Times
Table 2 Transit Times
Table 1 shows two-way ANOVA analysis that yields
no significant effects of sex and older siblings
on Static Rod rotation times.
Table 2 displays results of two-way ANOVA
analysis that yields a marginal effect of sex and
older sibling on Static Rod transit times.
Post-Hoc Multivariate General Linear Model on
Transit Times
Rod 2 25.6mm
Rod 3 19.5mm
Rod 1 31.1mm

References
Androgen Signaling
Maternal Response
1 Vincent, A., Deacon, R., Dalton, P., Salmond,
C., Blamire, A.M., Pendlebury, S., Johansen-Berg,
H., Rajogopalan, B., Styles, P., Stein, J.
(2002) Maternal antibody-mediated dyslexia?
Evidence for a pathogenic serum factor in a
mother of two dyslexic children shown by transfer
to mice using behavioral studies and magnetic
resonance spectroscopy. Journal of
Neuroimmunology, 130, 243-247. 2 Dalton, P.,
Deacon, R., Blamire, A., Pike, M., McKinlay, I.,
Stein, J., Styles, P., Vincent, A. (2003)
Maternal neuronal antibodies associated with
autism and a language disorder. Annual Neurology,
53, 533-537. 3 Blanchard, R. (2001) Fraternal
birth order and the maternal immune hypothesis of
male homosexuality. Hormone and Behavior, 40,
105-114.
Developmental Differences
Rod 5 9.4mm
Rod 4 15.4mm

• Individuals with these disorders have decreased
  motor coordination ranging from inability to
  control movement to deficiencies in fine motor
  movement.

Since there exists a marginal difference on
transit times when looking at sex and older
sibling, a post-hoc test was used to analyze a
linear model on transit times for each rod. The
initial results suggest that older sibling may
affect each sex differently. The multivariate
general linear model shows that in fact depending
on the sex, older sibling will affect transit
times differently. The difference between how
older siblings affected each sex approached
significant on Rod 1 (plt.1) and is significant on
Rod 4 (plt.05). plt.1 plt.05
Purpose
This is the first study to control the birth
order of mice in order to develop a model that
will examine the etiology of Autism, Dyslexia,
and Attention Deficit/Hyperactivity Disorder.
Acknowledgements
Methods

• Thanks to
• Breedlove/Jordan Lab, especially Janice Wong,
  Dave Putz, and Lace Svec for all their help
• McNair/SROP staff, especially Nettavia Curry,
  Roop Jayaraman, and Bethany Best
• Natural Science Methods Class
• This research project was funded by NIH grant
  MH58703

Conclusions
Subjects n110 Green Fluorescent Protein (GFP)
transgenic mice 61 males 25 with older
brothers, 36 with older sisters 49 females 20
with older brothers, 29 with older sisters

• Although it does not appear that fraternal birth
  order affect motor coordination, when post-hoc
  analyzes are run, significant interactions exist.
• The sex of older siblings affects each sex
  differently and that difference is significant on
  Rods 1 and 4.
• There may exist a significant difference on Rod
  1, not necessarily because of motor coordination,
  but rather due to motivation and understanding of
  the task. It may have taken male mice with older
  brothers longer to figure out the task.
• However, by the time mice are tested on Rod 4,
  they should have learned the task and be
  motivated to traverse the rod. Thus, Rod 4,
  because it is so thin, tests motor coordination
  better than the three previous rods and the
  differences that we see on Rod 4 are more likely
  due to differences in motor coordination.
• One note of interests is that females seem to be
  affected by fraternal birth order, as well, which
  is inconsistent with much of the research done in
  humans.

Imagine 1 Green Fluorescent Protein (GFP)
transgenic mice were breed at Van Andel. Male
mice carry a recessive protein marker on their
DNA that allows them to glow when exposed to UV
light. This allows for prenatal sexing of mice.